Slowly progressive aphasia without generalized dementia: studies with positron emission tomography

Slowly progressive aphasia without generalized dementia is a degenerative syndrome selectively affecting dominant hemisphere language areas. We report changes in regional glucose metabolism measured by positron emission tomography in two patients with this condition. Striking abnormalities of glucose utilization in the left cerebral cortex were demonstrated in both patients. The findings of other neurodiagnostic studies were relatively unremarkable. The first patient had a 3-year history of progressive anomia and impaired auditory verbal recall. An electroencephalogram was normal, and computed tomography showed mild left perisylvian atrophy. Positron emission tomography revealed profound hypometabolism in the left temporal regions. The second patient also had a 3-year history of progressive anomia. Electroencephalography, computed tomography, and magnetic resonance imaging scans were normal. Positron emission tomography showed a major reduction in left parietal glucose utilization, with a lesser decrement in left temporal metabolism. Neither patient demonstrated significant contralateral or global abnormalities such as those reported in positron emission tomographic studies of Alzheimer's disease with or without focal clinical features. These observations support the concept of adult-onset progressive aphasia without dementia as a clinical syndrome distinct from Alzheimer's disease.     

PET imaging of oncogene overexpression using 64Cu-vasoactive intestinal peptide (VIP) analog: comparison with 99mTc-VIP analog.

The purpose of this study was to assess the feasibility of PET imaging of oncogene VPAC1 receptors overexpressed in human breast cancer cells. METHODS: Vasoactive intestinal peptide (VIP) analog (TP3982) was synthesized to harbor a carboxy-terminus lysine (Lys) residue separated from VIP-asparagine (Asn(28)) by 4-aminobutyric acid (Aba) as a spacer. Lys was derivatized with diaminopropionic acid coupled to a pair of dibenzoylthioglycolic acid residues as protecting groups. The analog was labeled with (64)Cu at pH 9 ((64)Cu-TP3982) and (99m)Tc at pH 12 ((99m)Tc-TP3982). (99m)Tc-TP3982 and VIP derivatized with Aba-GAGG and labeled with (99m)Tc ((99m)Tc-TP3654) were used as reference agents. Smooth muscle relaxivity assays performed with each derivative and compared with unaltered VIP(28) demonstrated functional integrity. In vitro stability of (64)Cu-TP3982 was determined by challenging the complex with 100-mol excess of diethylenetriaminepentaacetic acid (DTPA), human serum albumin (HSA), and cysteine. In vivo stability was determined in urine and serum for up to 24 h. The mass of the Cu-TP3982 complex was determined by mass spectrometry. Human T47D breast tumor xenografts were grown in athymic nude mice. Planar scintigraphic imaging was performed at 4 and 24 h after the intravenous administration of (99m)Tc-TP3982 and (99m)Tc-TP3654 and PET imaging was performed using a small animal MOSAIC PET scanner, also at 4 and 24 h after injection of (64)Cu-TP3982. Tissue-distribution studies were also performed. In a separate experiment, receptors were blocked by intravenous injection of authentic VIP(28) 30 min before the administration of (64)Cu-TP3982 and tissue distribution was examined. RESULTS: (64)Cu-TP3982 labeling yields were 98% +/- 1.2% and those for (99m)Tc-TP3982 and (99m)Tc-TP3654 were 98.2% +/- 1.1% and 97% +/- 1.6%, respectively. The biologic activity of both VIP analogs was uncompromised. When (64)Cu-TP3982 was challenged with 100-mol excess of DTPA, HSA, or cysteine, >98% radioactivity remained as (64)Cu-TP3982. In vivo, >98% of (64)Cu circulating in plasma remained as (64)Cu-TP3982. Of the (64)Cu excreted in urine 4, 20, and 24 h after injection, >98%, 89.9% +/- 0.9%, and 85% +/- 3%, respectively, were bound to TP3982. The mass of Cu-TP3982 as determined by surface-enhanced laser desorption/ionization time of flight (SELDI-TOF) was 4,049.7 Da. Four hours after receptor blocking with VIP(28), there was a significant reduction in uptake of all tissues except in the liver. With (64)Cu-TP3982, the 4-h postinjection tumor uptake was 10.8 +/- 2.1 %ID/g versus 0.5 +/- 0.02 %ID/g and 0.24 +/- 0.08 %ID/g for (99m)Tc-TP3982 and (99m)Tc-TP3654, respectively. Twenty-four hours after injection, the corresponding numbers were 17 +/- 0.7 %ID/g, 0.77 +/- 0.1 %ID/g, and 0.23 +/- 0.1 %ID/g. The severalfold greater uptake (21.2-74) of (64)Cu-TP3982 is attributable to the in vivo stability of the agent. CONCLUSION: The results suggest that the uncompromised biologic activity and the significantly greater tumor uptake of (64)Cu-TP3982, combined with the high sensitivity and enhanced resolution of PET imaging, make (64)Cu-TP3982 highly desirable for further studies in PET imaging of oncogene receptors overexpressed in breast and other types of cancers.     

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

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The "liver scan" appearance in cholescintigraphy. A sign of complete common bile duct obstruction

One hundred consecutive Tc-99m IDA hepatobiliary scans were reviewed revealing 14 scans (14%), that showed nonvisualization of the common bile duct (CBD), gallbladder (GB), and small bowel (SB), but good hepatic uptake of Tc-99m IDA derivative, a pattern designated by us as "the liver scan appearance." In 11 of 14 cases (79%), the diagnosis of complete CBD obstruction was confirmed by surgery, percutaneous transhepatic cholangiogram (PTC), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous needle biopsy (PBx). Common bile duct obstruction was suspected but not proven in the other three cases. The cholescintigraphic, ultrasound, PTC, ERCP, intraoperative cholangiogram, clinical, laboratory, and surgical findings are presented and correlated. The "liver scan-appearance" by cholescintigraphy should suggest a diagnosis of complete common bile duct obstruction; however, it does not specifically differentiate between stone or tumor as the cause of obstruction.     

The Effect of Dietary Fibre on Gut Microbiota,Lipid Profile,and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background: A disequilibrium of the gut microbial community has been closely associated with systemic inflammation and metabolic syndromes including type 2 diabetes. While low fibre and high fat diets may lead to dysbiosis of the gut microbiome as a result of the loss of useful microbes, it has been reported that a high fibre diet may prevent the fermentation of protein and may promote eubiosis of gut microbiota. Aim: This review aims to evaluate the effect of dietary fibre (DF) on gut microbiota, lipid profile, and inflammatory markers in patients with type 2 diabetes. Methods: The PRISMA framework was relied on to conduct this systematic review and meta-analysis. Searches were carried out using electronic databases and reference list of articles. Results: Eleven studies were included in the systematic review, while ten studies were included in the meta-analysis. The findings revealed five distinct areas including the effects of DF on (a) gut microbiota (122 participants); (b) lipopolysaccharides (LPS, 79 participants) and lipopolysaccharides binding protein (LBP, 81 participants); (c) lipid profile; (d) inflammatory markers; and (e) body mass index (BMI, 319 participants). The relative abundance of Bifidobacterium increased by 0.73 (95% CI: 0.57, 0.89) in the DF group in contrast to the control (p < 0.05). With respect to LPS, the level was lower in the DF group than the control and the difference was significant (p < 0.05). The standardised mean difference for LPS was −0.45 (95% CI: −0.90, −0.01) although the difference between the two groups in relation to LBP was not significant (p = 0.08) and the mean difference was 0.92 (95% CI: −0.12, 1.95). While there was a decrease of −1.05 (95% CI: −2.07, −0.02) with respect to total cholesterol (356 participants) in the DF group as compared with the control (p < 0.05), both groups were not significantly different (p > 0.05) in the other lipid parameters. The difference between the groups was significant (p < 0.05) in relation to C-reactive protein, and the mean difference was 0.43 (95% CI: 0.02, 0.84). This could be due to the short duration of the included studies and differences in participants’ diets including the amount of dietary fibre supplements. However, the groups were not significantly different (p > 0.05) with respect to the other inflammatory markers. The meta-analysis of the BMI showed that the DF group decreased by −0.57 (95% CI: −1.02, −0.12) as compared with the control and this was significant (p < 0.01). Conclusion: DF significantly (p < 0.05) increased the relative abundance of Bifidobacterium and significantly decreased (p < 0.05) LPS, total cholesterol, and BMI as compared with the control. However, DF did not seem to have an effect that was significant on LBP, triglyceride, HDL cholesterol, LDL cholesterol, IL-6, TNF-α, adiponectin, and leptin. These findings have implications for public health in relation to the use of dietary fibre in nutritional interventions and as strategies for managing type 2 diabetes.     

Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats

Lasers in Medical Science - Diabetes mellitus is mostly interrelated to deficiency in wound healing. Low-level laser therapy has been shown to exert reliable effects on the acceleration of wound...     

Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway.

PURPOSE: Overexpression of eIF4E in surgical margins of head and neck cancer patients is an independent risk factor for recurrence. We hypothesize that overexpressed eIF4E is functionally active in tumor margins through activation of the Akt/mammalian target of rapamycin (mTOR) pathway EXPERIMENTAL DESIGN: Western blots and/or immunohistochemistry were performed to determine whether phosphorylation of mTOR and activation of its downstream molecules eIF4E-binding protein-1 (4E-BP1) and p70 S6 kinase and the upstream modulator of mTOR, Akt, were expressed in margins overexpressing eIF4E. RESULTS: There was a significant association between phospho-4E-BP1 and eIF4E expression of a margin or a significant difference in phospho-4E-BP1 expression between the eIF4E-positive and -negative margins (P < 0.01). A significant association between eIF4E and phospho-p70 S6 kinase as well as eIF4E and phospho-mTOR was also noted (P < 0.05). Western blot analysis indicated a highly significant difference in the phosphorylation status of 4E-BP1 between tumors and resection margins. A total of 89% of the 4E-BP1-expressing margins expressed more of the phosphorylated (beta, gamma, and delta) isoforms, whereas 81% of the 4E-BP1-expressing tumors expressed more of the unphosphorylated alpha isoform. A similar difference in Akt activation was noted between eIF4E-positive margins and tumors (P < 0.05). CONCLUSIONS: Overexpression of eIF4E is functionally active in tumor margins through activation of the Akt/mTOR signaling pathway. The greater degree of expression of downstream targets and upstream regulators of mTOR in margins compared with the tumors indicates preferential activation of the Akt/mTOR signaling pathway in margins overexpressing eIF4E. Rapamycin analogs can potentially be used as adjuvant therapy for patients with eIF4E-positive margins.