Safety of percutaneous versus transjugular liver biopsy: A propensity score matched analysis.

PURPOSE: This study sought to identify the complication, mortality, and readmission rates of patients undergoing either percutaneous (PCLB) or transjugular liver biopsy (TJLB) when propensity matched for demographics and hepatic comorbidities. METHODS: A retrospective review of New York's Statewide Planning and Research Cooperative System ICD9 coded database from the years 2009-2013 was conducted. Patients over the age of 18 undergoing either PCLB or TJLB were included. Patients with hepatic neoplasm or metastasis were excluded. 2:1 PCLB:TJLB propensity match for age, race, payment, coagulopathy, thrombocytopenia/purpura, hypercoagulability, ascites, acute liver failure, chronic hepatitis, cirrhosis, and bone marrow disease was conducted. Univariate analysis compared demographics, complications, readmissions, and mortality. RESULTS: 1467 patients met inclusion criteria (PCLB = 978, TJLB = 489). Propensity match was successful in that there were no significant differences in demographics or hepatic comorbidities. TJLB had significantly lower rates of hematoma (0.20 % vs 1.20 %, p = 0.049) and higher rates of cardiac complications (0.40 % vs 0.00 %, p = 0.045). Other complication, readmission, and mortality rates did not differ significantly. Logistic regression found no significant predictors of readmission within 7 days or any complication within 5 days. CONCLUSION: This retrospective, multi-center database review of adult patients undergoing PCLB or TJLB propensity matched for demographics and hepatic comorbidities found that TJLB patients had a significantly higher rate of cardiac complications while PCLB patients had a significantly higher rate of hematoma. These findings support prior literature suggesting a trend towards safety of TJLB compared to PCLB in patients with hemostatic disorders and/or advanced liver disease.

A systematic review of automated feeder detection software for locoregional treatment of hepatic tumors.

PURPOSE: The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using automated feeder detection (AFD) software. MATERIALS AND METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD software. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional digital subtraction angiography (DSA) and cone-beam CT (CBCT) without AFD. RESULTS: A total of 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients (305 men, 156 women; mean age, 68.6±6.0 [SD] years), including 537 patients with hepatocellular carcinoma, 8 with metastases from neuroendocrine tumors, and 59 patients without reported etiology. Reported sensitivity of AFD ranged between 86% and 98.5%, compared to DSA alone (38% - 64%) or DSA in combination with CBCT (69% - 81%). Three studies reported tumor response by modified response evaluation criteria in solid tumors (mRECIST) guidelines, with complete response in the range of 60% - 69%. CONCLUSION: AFD is a promising new technology for the identification of intrahepatic and extrahepatic tumor-feeding arteries and should be considered a useful adjunct to conventional DSA and CBCT in the treatment of liver tumors.

Terapia combinada de levotiroxina y liotironina para hipotiroidismo / Combined therapy with levothyroxine and liothyronine for hypothyroidism

INTRODUCCIÓN La suplementación habitual del hipotiroidismo se basa en la monoterapia con levotiroxina, sin embargo, algunos pacientes persisten con síntomas atribuibles al déficit de hormona tiroidea. Debido a esto se ha planteado que el uso de un tratamiento combinado con liotironina y levotiroxina otorgaría un mayor beneficio. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos tres revisiones sistemáticas que en conjunto incluyeron 12 estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que la adición de liotironina al tratamiento del hipotiroidismo tiene un efecto mínimo o nulo sobre fatiga y calidad de vida. Probablemente tampoco mejora estado de ánimo, dolor ni función cognitiva, y no reduciría el peso corporal.

INTRODUCTION The usual supplementation for hypothyroidism is based on monotherapy with levothyroxine. However, some patients persist with symptoms attributable to the deficit of thyroid hormone. It has been suggested that the a combined treatment with liothyronine and levothyroxine would provide a greater benefit. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified three systematic reviews including twelve primary studies overall, all of which were randomized trials. We concluded that the addition of liothyronine to the treatment of hypothyroidism has minimal or no effect on fatigue and quality of life. It probably does not improve mood, pain or function cognitive, and it would not reduce body weight.

Two-year outcomes of balloon-occluded retrograde transvenous obliteration of gastric varices in liver transplant recipients: A multi-institutional study.

PURPOSE: To assess the 2-year effectiveness and safety of balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GVs) in liver transplant recipients. MATERIALS AND METHODS: Eleven liver transplant recipients underwent consecutive BRTO for GVs at four institutions. Patients included eight (73%) men and three (27%) women with mean age of 56 years±12 (SD) (range: 26-67 years). Underlying cause of liver transplantation was hepatitis C virus (HCV)-related cirrhosis in five (45%), alcohol- and HCV-related cirrhosis in three (27%), primary biliary cirrhosis in two (18%), and alcoholic cirrhosis in one (9%). Five (45%) patients underwent BRTO for actively bleeding GVs, three (17%) for high-risk GVs, and three (17%) for augmentation of portal venous flow through obliteration of gastrorenal shunts. Mean time between liver transplantation and BRTO was 78 months (range: 0.1-276 months). Technical success, GVs obliterative rates, and immediate complications were recorded. Post-BRTO hemorrhagic, transplant, and overall survival rates were evaluated at 6, 12, and 24 months. RESULTS: All (100%) procedures were technically successful. Complete GVs obliteration was achieved in ten patients (91%). Two major complications (18%) occurred in the immediate post-procedure period. One patient developed complete portal vein thrombosis, and another patient developed consumptive coagulopathy, ultimately leading to death. No post-BRTO hemorrhagic recurrences were seen at 6, 12, or 24 months. One patient (9%) had delayed upper gastrointestinal bleeding at 34 months after the procedure which was managed conservatively. Transplant and overall survival rates were 91% at 6, 12, and 24 months. CONCLUSION: BRTO has high technical success and complete GVs obliterative rates in liver transplant recipients with few complications and high graft survival rates.

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia.

PURPOSE: Transradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions. METHODS AND MATERIALS: Patients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications. RESULTS: From July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6% with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9%) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1%) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups. CONCLUSIONS: Transradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

Tailoring the endovascular management of transplant renal artery stenosis.

In this study we analyze the different types of endovascular interventions (EVIs) in de novo transplant renal artery stenosis (TRAS) and its anatomical subtypes to examine any variation in recovery of allograft function, blood pressure control, EVI patency and allograft survival with respect to EVI type (DES: drug-eluting stent, BMS: bare-metal stent, PTA: percutaneous transluminal angioplasty). Forty-five patients underwent a total of 50 primary EVIs (DES: 18, BMS: 26, PTA: 6). Patients were stratified according to medical co-morbidities, graft characteristics, biopsy results, clinical presentation and TRAS anatomic subtypes (anastomotic: 26, postanastomotic: 17, bend-kink: 2). There was significant improvement in allograft function and mean arterial blood pressure (MAP) control across all interventions (pre-EVI-creatinine [CR]: 2.8 ± 1.4, post-EVI-Cr: 2.1 ± 0.7, p < 0.001; pre-EVI-MAP: 117 ± 16, post-EVI-MAP: 112 ± 17, p = 0.03) with no significant difference among EVI types. There was no significant difference in allograft survival with respect to EVI type. Patency was significantly higher in EVIs performed with DES and BMS compared to PTA (p = 0.001). In the postanastomotic TRAS subtype, patency rates were significantly higher in DES compared to BMS (p = 0.012) in vessels of comparable reference diameter (≤5 mm).

Chemoembolization with drug-eluting microspheres (DEM-TACE) for hepatocellular carcinoma: single-center review of safety and efficacy.

PURPOSE: This study examines the safety and efficacy of transarterial chemoembolization using doxorubicin-loaded 30-60 µm QuadraSphere microspheres (DEM-TACE) for the treatment of hepatocellular carcinoma. MATERIALS AND METHODS: Over 10 weeks, patients with hepatocellular carcinoma. (Child-Pugh A/B: 65%/35%) were embolized with 30-60 µm QuadraSphere microspheres. Excluded patients had previous locoregional therapy, macrovascular invasion, extrahepatic disease, Child-Pugh score >B7, ECOG performance status >0, and total bilirubin >3 mg/dL. Technical success, minor and major complications, 30-day hospital readmission rate, and 30-day mortality were assessed. α-Fetoprotein levels before and after treatment were compared. Local response was evaluated by radiologic tumor response per modified Response Evaluation Criteria in Solid Tumors 1 month after treatment. RESULTS: Thirty tumors (mean size, 2.3 cm; range, 1.0-4.9 cm) were treated in 20 patients (16 male and 4 female; mean age, 64.7 years). There were no major complications. Thirty-day mortality was 0%. Minor complications included postembolization syndrome in 16.7% of cases and transient rise in liver enzymes requiring no therapy. Mean α-fetoprotein levels trended down following treatment (71.8±201.9 ng/mL vs 53.4±116.7 ng/mL), but were not statistically significant. Complete response was achieved in 30% of patients, partial response in 35%, stable disease in 30%, and progression of disease in 5%. Overall objective response was 65%. Mean follow-up was 10.4 months (range, 2-16.4 months). CONCLUSION: DEM-TACE with doxorubicin-loaded 30-60 µm QuadraSpheres is feasible, well tolerated, and associated with promising tumor response in early and intermediate stage disease.

Nitric oxide activates intradomain disulfide bond formation in the kinase loop of Akt1/PKBα after burn injury.

Severe burn injury is an acute inflammatory state with massive alterations in gene expression and levels of growth factors, cytokines and free radicals. During the catabolic processes, changes in insulin sensitivity and skeletal muscle wasting (unintended loss of 5-15% of lean body mass) are observed clinically. Here, we reveal a novel molecular mechanism of Akt1/protein kinase Bα (Akt1/PKBα) regulated via cross-talking between dephosphorylation of Thr308 and S-nitrosylation of Cys296 post severe burn injury, which were characterized using nano-LC interfaced with tandem quadrupole time-of-fight mass spectrometry (Q-TOF)micro tandem mass spectrometry in both in vitro and in vivo studies. For the in vitro studies, Akt1/PKBα was S-nitrosylated with S-nitrosoglutathione and derivatized by three methods. The derivatives were isolated by SDS-PAGE, trypsinized and analyzed by the tandem MS. For the in vivo studies, Akt1/PKBα in muscle lysates from burned rats was immunoprecipitated, derivatized with HPDP-Biotin and analyzed as above. The studies demonstrated that the NO free radical reacts with the free thiol of Cys296 to produce a Cys296-SNO intermediate which accelerates interaction with Cys310 to form Cys296-Cys310 in the kinase loop. MS/MS sequence analysis indicated that the dipeptide, linked via Cys296-Cys310, underwent dephosphorylation at Thr308. These effects were not observed in lysates from sham animals. As a result of this dual effect of burn injury, the loose conformation that is slightly stabilized by the Lys297-Thr308 salt bridge may be replaced by a more rigid structure which may block substrate access. Together with the findings of our previous report concerning mild IRS-1 integrity changes post burn, it is reasonable to conclude that the impaired Akt1/PKBα has a major impact on FOXO3 subcellular distribution and activities.

Isolation rearing significantly perturbs brain metabolism in the thalamus and hippocampus.

Psychosocial neglect during childhood severely impairs both behavioral and physical health. The isolation rearing model in rodents has been employed by our group and others to study this clinical problem at a basic level. We previously showed that immediate early gene (IEG) expression in the hippocampus and medial prefrontal cortex (mPFC) is decreased in isolation-reared (IR) compared to group-reared (GR) rats. In the current study, we sought to evaluate: (1) whether these changes in IEG expression would be detected by the measurement of brain glucose metabolism using positron emission tomography (PET) with fluorodeoxyglucose (FDG) and (2) whether PET FDG could illuminate other brain regions with different glucose metabolism in IR compared to GR rats. We found that there were significant differences in FDG uptake in the hippocampus that were consistent with our findings for IEG expression (decreased mean FDG uptake in IR rats). In contrast, in the mPFC, the FDG uptake between IR and GR rats did not differ. Finally, we found decreased mean FDG uptake in the thalamus of the IR rats, a region we had not previously examined. The results suggest that PET FDG has the potential to be utilized as a biomarker of molecular changes in the hippocampus. Further, the differences found in thalamic brain FDG uptake suggest that further investigation of this region at the molecular and cellular levels may provide an important insight into the neurobiological basis of the adverse clinical outcomes found in children exposed to psychosocial deprivation.

Delivery of proteins to CNS as seen and measured by positron emission tomography.

Presently, there are no effective treatments for several diseases involving the central nervous system (CNS). While several novel molecular approaches are being developed, many of them require delivery of macromolecular or supramolecular agents to the CNS tissues protected by the blood-brain and blood-arachnoid barriers. A variety of approaches that are being developed for overcoming or bypassing the barriers are based on complex transfer processes. The delivery of biopharmaceuticals and other macromolecules and particulates to the CNS, especially through the leptomeningeal (intrathecal) route, includes a variety of stages, such as leptomeningeal propagation, drainage to the systemic circulation, and penetration into the CNS. The investigation of complex pharmacokinetics that includes convective, as well as diffusional and active transfer processes, greatly benefit from real-time non-invasive in vivo monitoring of the drug transport. Pharmacological positron emission tomography (PET) imaging, which enables such monitoring, plays an increasingly significant role in drug delivery and biopharmacology. PET is a powerful tool for quantitative in vivo tracking of molecules labeled with positron-emitting radionuclides. The high sensitivity, format, and accuracy of the data (similar to those of conventional tissue sampling biodistribution studies) make PET a readily adoptable pharmacological technique. In contrast to the conventional studies, PET also allows for longitudinal nonterminal same-animal studies. The latter may not only improve the data statistics, but also enable preclinical studies (especially in large and/or rare animals) not feasible under the conventional approach. This paper is intended to demonstrate the character of data that can be obtained by PET and to demonstrate how the main patterns of the leptomeningeal route pharmacokinetics can be investigated using this method. Examples of data processing are taken from our recent studies of five model proteins in rats and nonhuman primates.

Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates.

Presently, there are no effective treatments for conditions characterized by protein misfolding, such as Alzheimer's, Parkinson's, and other diseases involving CNS. Since misfolding occurs at the earliest stage of the disease, it is likely to be involved in subsequent pathological developments. It has been found that NPT002 (bacteriophage M13) directly dissociates aggregates of misfolded proteins that form amyloid, including amyloid-ß, tau and α-synuclein. For CNS applications, NPT002 requires delivery to the brain parenchyma, the target tissue. NPT002 is an elongated ~950 nm particle that cannot penetrate into the brain from the blood. Furthermore, phage particles, due to their size, cannot be effectively transported in vivo by diffusion. Considering the physiology of the leptomeningeal space, intrathecal administration appears to be a promising convection-driven avenue for NPT002 delivery. In this paper, we use positron emission tomography to investigate the transport of NPT002 in Macaca fascicularis. The data suggest that approximately 50 % of the administered dose can reach the cerebral leptomeningeal space after a single lumbar intrathecal injection. A biologically significant fraction of the phage then enters the brain, resulting in potentially therapeutic cortical and subcortical exposure.

SILAM for quantitative proteomics of liver Akt1/PKBα after burn injury.

Akt1/protein kinase Bα (Akt1/PKBα) is a downstream mediator of the insulin signaling system. In this study we explored mechanism(s) for its role in burn injury. Akt1/PKBα in liver extracts from mice with burn injury fed with (2H7)-L-Leu was immunoprecipitated and isolated with SDS-PAGE. Two tryptic peptides, one in the kinase loop and a control peptide just outside of the loop were sequenced via nano-LC interfaced with quadruple time-of-flight tandem mass spectrometry (Q-TOF tandem MS). Their relative isotopologue abundances were determined by stable isotope labeling by amino acids in mammalians (SILAM). Relative quantifications based on paired heavy/light peptides were obtained in 3 steps. The first step included homogenization of mixtures of equal amounts of tissue from burned and sham-treated animals (i.e., isotope dilution) and acquisition of uncorrected data based on parent monoisotopic MS ion ratios. The second step included determination of isotopic enrichment of the kinase from burned mice on Day 7 and the third step enrichment correction of partially labeled heavy and light monoisotopic MS ion ratios for relative quantification of bioactivity (loop peptide) and expression level (control peptide). Protein synthesis and enrichment after injury were found to be dependent on tissue and turnover of individual proteins. Three heavy and light monoisotopic ion ratios for albumin peptides from burned mice indicated ~55% enrichment and ~16.7-fold downregulation. In contract, serum amyloid P had ~66% enrichment and was significantly upregulated. Akt1/PKBα had ~56% enrichment and kinase level in response to the burn injury was upregulated compared with the control peptide. However, kinase bioactivity, represented by the Cys296 peptide, was significantly reduced. Overall, we demonstrated that i) quantitative proteomics can be performed without completely labeled mice; ii) measurement of enrichment of acyl-tRNAs is unnecessary and iii) Cys296 plays an important role in kinase activity after burn injury.

Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder.

BACKGROUND: Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events. METHOD: Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events. RESULTS: Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately. CONCLUSIONS: Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

Value of drug-eluting stents after failed percutaneous transluminal angioplasty in the infrapopliteal vessels for the treatment of critical limb ischemia: favorable mid-term patency and limb salvage results.

AIM: The endovascular treatment of infrapopliteal arterial disease in the setting of critical limb ischemia (CLI) is increasing in use. In patients in whom percutaneous transluminal angioplasty (PTA) resulted in suboptimal angiographic results, flow limiting dissection or re-coil is thought to limit clinical success. This single-center experience examines the angiographic and clinical results when Drug-Eluting Stents (DES) were placed in a large cohort of patients with CLI after immediate infrapopliteal PTA failure. METHODS: A retrospective review of a prospectively collected single-center endovascular database was performed. Sixty-seven Rutherford grade 4, 5, and 6 patients were treated between October 2005 and February 2010 with PTA because lack of an acceptable autologous vein for bypass-grafting or severe medical comorbidities precluded them from surgical bypass. The study cohort had suboptimal angiographic results immediately after PTA that was subsequently treated with DES. Patients were then placed on clopidogrel and aspirin indefinitely. Angiographic, clinical, and the results of noninvasive vascular examinations were collected. RESULTS: In total, 123 stents (94 sirolimus, 27 everolimus, 2 paclitaxel) were placed in 67 patients to treat a total of 84 angiographic lesions. Simultaneous femoral-popliteal intervention was performed in 66% of the patients while 45% of the treated lesions were total occlusions. Lesion length ranged from 17 mm-142 mm (mean 50 mm). Initial technical success was 100%, with all 84 lesions being treated successfully with less than 10% stenosis after stent implantation. Mean follow-up was 20 months (1-42 months) with 6, 12, and 24-month primary patency rates of 90%, 86%, and 72% respectively. Freedom from major amputation was 91.1% (61/67) with all six amputations occurring in the Rutherford grade 6 group (6/11). Overall mortality rate was 19% (13/67) with one death occurring within 30 days. CONCLUSION: The use of drug-eluting stents following suboptimal PTA for the treatment of infrapopliteal arterial disease in this cohort of patients with CLI produced high primary patency and limb salvage rates supporting the efficacy of this treatment strategy.

Imaging amyloid deposition in Lewy body diseases.

BACKGROUND: Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD). OBJECTIVES: To determine whether amyloid deposition, as assessed by PET imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features. METHODS: Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio. RESULTS: Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function. CONCLUSIONS: Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that beta-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

Psychosis of Alzheimer's disease: Gender differences in regional perfusion.

We sought to determine whether the presence of psychotic symptoms in patients with Alzheimer's disease is associated with abnormal regional cerebral function. Perfusion single photon emission computed tomography images from 51 AD patients with psychotic symptoms were compared to images of 52 AD patients without such symptoms. Group comparisons were made with a voxel-based method, Statistical Parametric Mapping. We found that perfusion was lower in female patients with psychotic symptoms in right infero-lateral prefrontal cortex and in inferior temporal regions compared to female patients without such symptoms. In contrast, perfusion was higher in male patients with psychotic symptoms in the right striatum compared to male patients without such symptoms. Comparison groups did not differ in age or in dementia severity, as estimated by the Mini-Mental State Examination (MMSE). These results support the role of right hemisphere prefrontal and lateral temporal cortex in the psychosis of AD in women but not in men, and raise the possibility that these dysfunctional processes have a gender-specific regional pathophysiology in AD.

Single photon emission computed tomography perfusion differences in mild cognitive impairment.

OBJECTIVE: To relate cerebral perfusion abnormalities to subsequent changes in clinical status among patients with mild cognitive impairment (MCI). METHODS: Perfusion single photon emission computed tomography (SPECT) images were acquired in 105 elderly patients without dementia with MCI, using 99mTc-HMPAO. Clinical outcome after a 5-year follow-up period was heterogeneous. RESULTS: Baseline SPECT data differed in those patients with MCI who were later diagnosed with Alzheimer's disease (the converter group) from those patients with MCI who experienced clinically evident decline but did not progress to a diagnosis of Alzheimer's disease within the follow-up period (the decliner group), from patients with MCI who had no clinical evidence of progression (the stable group), and from a group of 19 normal subjects (the control group). The most consistent decreases in relative perfusion in converters compared with the normal, stable and decliner groups were observed in the caudal anterior cingulate, and in the posterior cingulate. In addition, converters showed increased relative perfusion in the rostral anterior cingulate in comparison to the stable and decliner groups. A group of patients with Alzheimer's disease were also included for purposes of comparison. The group of patients with Alzheimer's disease at baseline differed from each of the other groups, with temporoparietal regions showing the most significant reductions in perfusion. CONCLUSIONS: These results suggest that clinical heterogeneity in MCI is reflected in SPECT perfusion differences, and that the pattern of perfusion abnormalities evolves with increasing clinical severity.

Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

Laparoscopic scar: a mimicker of Sister Mary Joseph's nodule on positron emission tomography/CT.

Positron emission tomography/CT is an established imaging method in the diagnosis and staging of cancers. (18)F-fluoro-2-deoxy-d-glucose (FDG) is the most commonly used radiotracer in positron emission tomography/CT. It is a tumour viability agent and usually its uptake within a lesion reflects the presence of a viable tumour tissue. However, false-positive FDG uptake is known to occur in benign processes of either inflammatory or infectious aetiology. We describe FDG uptake at the site of laparoscopic scar that mimicked Sister Mary Joseph's nodule in a patient with gastric adenocarcinoma. Here, the knowledge of the patient's history and subtle imaging findings helped in accurate staging of the patient. In this case report, we emphasize the value of the knowledge of the patient history and awareness of different pitfalls of FDG to achieve a correct diagnosis on positron emission tomography/CT.

Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy.

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU x m(-2) x min(-1)) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-D-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 +/- 0.4 vs. 2.3 +/- 0.5 micromol x kg tissue(-1) x min(-1), P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal (r2 = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area (r = -0.75, P = 0.008), and whole body glucose disposal (r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.