Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study

Annals of Nuclear Medicine - Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of...     

Effect of kihito extract granules on cognitive function in patients with Alzheimer's-type dementia

Background:   It has been recently suggested that Japanese herbal (kampo) medicines, such as kami-untan-to, may improve cognitive function in elderly subjects with Alzheimer's disease. Polygalae radix is thought to be a useful component of kami-untan-to because it enhances the activity of choline acetyltransferase in cultured neuronal cells. The purpose of the present study was to investigate the safety and usefulness of kihito extract granules, a commercially available Japanese herbal medicine that contains P. radix , for elderly patients with senile dementia.
Methods:   Seventy-five elderly subjects (84.4 ± 6.4 years) with senile dementia of Alzheimer type according to Diagnostic and Statistical Manual of Mental Disorders , 4th edition criteria were randomly assigned to the non-treatment, goshajinkigan (control kampo medicine) or kihito groups. Each medicine was given three times a day for 3 months.
Results:   There was no severe adverse event in any of the groups. We examined the Mini-Mental State Examination (MMSE), the activities of daily living (ADL) scale and cerebrovascular single photon emission computed tomography (SPECT) before and after treatment. MMSE scores were significantly improved only in the kihito group (+1.65 ± 0.53) but not in the non-treatment (−0.3 ± 0.67) and goshajinkigan (−0.58 ± 0.49) groups. ADL scores remained unchanged in all groups. Treatment with kihito was not associated with an increase in cerebral blood flow.
Conclusion:   These results propose that kihito may be useful and has potential to be tested as a medicine for Alzheimer's-type senile dementia, although further examination is required to clarify the mechanism of the improving effect of kihito on cognitive function.     

Long-term follow up of esophageal varices after balloon-occluded retrograde transvenous obliteration for gastric varices.

Aim: Because the procedure of balloon-occluded retrograde transvenous obliteration (B-RTO) causes extensive thrombosis of the major shunt that connects the spleen and gastric/renal venous systems, an increase in portal pressure is unavoidable. The aim of the present study was to assess the long-term outcome of B-RTO, including changes in esophageal varices. Methods: B-RTO was conducted in 22 patients with gastric varices, who were divided according to the severity of esophageal varices at baseline; there were no esophageal varices (n = 7), F(1) varices (n = 11), and F(2) varices (n = 4). The outcome measures included the development/worsening of esophageal varices after B-RTO and survival rates. Results: The cumulative bleeding-free probability for all 22 patients at 3 years after B-RTO was 100%. The overall 3-year survival was 94.4%. Seven patients who had no esophageal varices prior to B-RTO did not develop any after the procedure. Seven (63.6%) of the 11 patients with stage F(1) esophageal varices prior to B-RTO showed no changes in the varices after B-RTO, while two patients progressed to F(2) varices and two developed F(3) varices. The cumulative treatment-free probability of the esophageal varices at 24 months after B-RTO was 100% for patients without esophageal varices at baseline, 80.8% for patients with pre-existing F(1) varices, and 75% for those with pre-existing F(2) varices. Conclusion: Although the B-RTO procedure is considered useful for the treatment of gastric varices, changes in hemodynamics due to obliteration of this major shunt must be taken into account and observed closely.     

Reversible stenosis of large cerebral arteries in a patient with combined Sjögren’s syndrome and neuromyelitis optica spectrum disorder

We report a 49-year-old woman with neuromyelitis optica (NMO) spectrum disorder coexisting with Sj?gren's syndrome (SS). She presented with acute brainstem symptoms and transverse myelitis. Brain MRI showed focal high signal intensity lesions in the hypothalamus and the pontine tegmentum on T2-weighted and FLAIR images. MRA revealed stenotic changes of the bilateral middle cerebral artery (MCA), posterior cerebral arteries (PCA) and basilar artery (BA). Spinal MRI revealed hyperintense lesions within the cord extending from the T4 to the T6 level on the T2-weighted image. The patient fulfilled the clinical criteria of primary SS. In addition, anti-AQP4 antibody which is highly specific for NMO was detected in the serum at the acute phase. The patient excellently responded to IVIg while methylprednisolon pulse therapy was not effective. Follow-up MRA displayed complete resolution of the stenosis of the MCA, PCA and BA.     

Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages

Objectives:   Macrophages (Mφs) have various functions and play a critical role in host defense and the maintenance of homeostasis. Mφs exist in every tissue in the body, but Mφs from different tissues exhibit a wide range of phenotypes with regard to their morphology, cell surface antigen expression and function, and are called by different names. However, the precise mechanism of the generation of macrophage heterogeneity is not known. In the present study, the authors examined the functional heterogeneity of Mφs generated from human monocytes under the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF).
Methodology:   CD14 positive human monocytes (Mos) were incubated with M-CSF and GM-CSF for 6–7 days to stimulate the generation of M-CSF-induced monocyte-derived Mφs (M-Mφs) and GM-CSF-induced monocyte-derived Mφs (GM-Mφs), respectively. The expression of cell surface antigens and several functions such as antigen presenting cell activity, susceptibility to oxidant stress, and the susceptibility to HIV-1 and mycobacterium tuberculosis infection were examined.
Results:   GM-Mφs and M-Mφs are distinct in their morphology, cell surface antigen expression, and functions examined. The phenotype of GM-Mφs closely resembles that of human Alveolar-Mφs (A-Mφs), indicating that CSF-induced human monocyte-derived Mφs are useful to clarify the molecular mechanism of heterogeneity of human Mφs, and GM-Mφs will become a model of human A-Mφs.     

An autopsy case of granulocyte-colony-stimulating-factor-producing extrahepatic bile duct carcinoma

A 79-year-old man was referred to this department due to the presence of extrahepatic bile duct carcinoma with a tumor at the left chest wall. The lesion was suspected to be a metastasis of bile duct carcinoma to the left wall, however, computed tomography （CT） revealed no regional lymph node or liver metastases. In addition, cytological and pathological examinations did not show malignancy. At the time of admission, the white blood cell count was 21 460 cells/μL （neutrophils, 18 240 cells/μL） and this elevated to 106 040 before death. In addition, serum granulocyte colony-stimulating factor （G-CSF） was elevated. At 28 d after admission, the patient died. An autopsy showed a poorly differentiated adenocarcinoma with sarcomatous change, which had slightly invaded into the pancreas around the bile duct, and was found in the distal bile duct with multiple metastases to the chest wall, lung, kidney, adrenal body, liver, mesentery, vertebra and mediastinal and para-aortic lymph nodes, without locoregional lymph node and liver metastasis. The cancer cells showed positive immunohistochemical staining for anti-G-CSF antibody. This is believed to be the first report of an extrahepatic bile duct carcinoma that produces G-CSF. Since G-CSF-producing carcinoma and sarcomatous change of the biliary tract leads to poor prognosis, early diagnosis and treatment are needed. When infection is ruled out, the G-CSF in serum should be examined. In addition, examinations such as bonescintigraphy and chest CT should also be considered for distant metastasis.     

Preload-adjusted 2 wave-intensity peaks reflect simultaneous assessment of left ventricular contractility and relaxation.

BACKGROUND: The magnitudes of the first (WI1) and the second wave-intensity peak (WI2) during the ejection period can be used as indices of left ventricular (LV) contractility and relaxation, respectively. However, use of WI to characterize LV dp/dt and the end-diastolic volume (V ed) relationship may be more problematic, as WI may be affected by changes in preload. METHODS AND RESULTS: The LV pressure-volume data sets, consisting of 23 recordings obtained by the conductance method from 12 heart disease patients, were studied. End-systolic elastance (E es) and volume-axis-intercept (V0) were calculated with varying preload. Time constant of LV relaxation (tau), V ed, and WI were calculated from steady-state averaged data. The E es showed a weak correlation with WI1 (r = 0.46, p < 0.05) but a better correlation with preload-adjusted WI1 [WI1/V ed; r=0.86, WI1/V(ed)2; r = 0.92, WI1/(V ed - V0)2; r = 0.89, all p < 0.01]. Similarly, tau did not correlate with WI2 but did correlate with preload-adjusted WI2 [WI2/V ed; r = -0.73, WI2/V(ed) 2; r = -0.63, WI2/(V ed - V0)2; r = -0.78, all p < 0.01]. CONCLUSIONS: These data demonstrate the importance of preload-adjustment when using the WI index for simultaneous assessment of LV contractility and relaxation.     

Improvement of endothelial dysfunction by angiotensin II blockade accompanied by induction of vascular hepatocyte growth factor system in diabetic spontaneously hypertensive rats

 Hepatocyte growth factor (HGF) is a unique growth factor with many protective functions. Previously, we demonstrated that HGF stimulated growth of endothelial cells without replication of vascular smooth muscle cells (VSMC) and that angiotensin (Ang) II significantly decreased local HGF production in VSMC. Moreover, we also reported that high glucose significantly decreased local vascular HGF production. Therefore, we examined effects of Ang II blockade on vascular HGF expression and endothelial injury in diabetic hypertensive rats. An angiotensin-converting enzyme inhibitor (quinapril) and an Ang II type 1 receptor antagonist (GA-0113) or vehicle was administrated to diabetic spontaneously hypertensive rats (SHR-DM), in whom diabetes was induced by streptozotocin. Endothelial function was evaluated by the vasodilator response to acetylcholine, and the expression of vascular HGF and its receptor, c-met, was examined by immunohistochemistry. Both quinapril and GA-0113 significantly improved the vasodilator response to acetylcholine (P < 0.01), while vehicle did not as compared to untreated normotensive Wistar-Kyoto rats (WKY). We next examined the effects of Ang II blockade on vascular HGF expression in SHR-DM. Importantly, the vascular HGF level was markedly decreased in SHR-DM as compared to WKY, while Ang II blockade by quinapril or GA-0113 significantly increased positive staining for HGF in SHR-DM. Similarly, staining of its specific receptor, c-met, was less in the blood vessels of SHR-DM as compared to WKY. In contrast, Ang II blockade also significantly increased c-met production in SHR-DM. The present data demonstrated the improvement of endothelial dysfunction by Ang II blockade in SHR-SM, accompanied by an increase in vascular HGF and c-met. Received: June 7, 2002 / Accepted: September 21, 2002 Acknowledgments We wish to thank Rie Kosai and Keiko Yamaguchi for their excellent technical assistance. This work was partially supported by grants from the Japan Health Sciences Foundation, a Grant-in-Aid from The Ministry of Public Health and Welfare, a Grant-in-Aid for the Development of Innovative Technology, a Grant-in-Aid from Japan Promotion of Science, and through Special Coordination Funds of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. Correspondence to N. Tomita