Inferior Vena Cava Filter Evaluation and Management for the Diagnostic Radiologist: A Comprehensive Review Including Inferior Vena Cava Filter-Related Complications and PRESERVE Trial Filters

Inferior vena cava filters are commonly encountered devices on diagnostic imaging that were highlighted in a 2010 Food and Drug Administration safety advisory regarding their complications from long-term implantation. The Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE) trial is an ongoing after-market study investigating the safety and utility of commonly utilized filters in practice today. While most of these filters are safe, prompt recognition and management of any filter-associated complication is imperative to prevent or reduce the morbidity and mortality associated with them. This review is aimed at discussing the appropriate utilization and placement of inferior vena cava filters in addition to the recognition of filter-associated complications on cross-sectional imaging. An overview of the PRESRVE trial filters is also provided to understand each filter's propensity for specific complications.     

In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease

Aims

The aims of this study were to visualize in vivo binding of donepezil to acetylcholinesterase (AChE) in the brain and to establish a method for measuring the amount of binding of orally administered donepezil.

Methods

[5-¹¹C-methoxy]-donepezil ([¹¹C]-donepezil) was radiolabelled as a positron emission tomography (PET) tracer. The biodistribution of [¹¹C]-donepezil was measured by PET in 10 AD patients and six elderly normal subjects. Two AD patients underwent additional PET measurements after oral administration of donepezil for 6 months.

Results

[¹¹C]-donepezil-PET images demonstrated high densities of tracer distribution in AChE-rich brain regions such as the striatum, thalamus, and cerebellum. Compared with elderly normal subjects, patients with mild AD exhibited about 18–20% reduction of donepezil binding in the neocortex and hippocampus, while patients with moderate AD exhibited about 24–30% reduction of donepezil binding throughout the brain. Orally administered donepezil (5 mg day⁻¹) induced 61.6–63.3% reduction of donepezil binding in AD brains. The distribution volume of [¹¹C]-donepezil in the hippocampus was significantly correlated with MMSE scores in AD patients.

Conclusions

[¹¹C]-donepezil-PET enables quantitative measurement of donepezil binding in the brain. AD patients exhibited reduction of donepezil binding in the brain, even in the early stage of disease. Longitudinal evaluation by this technique enables determination of AChE binding occupancy of orally administered donepezil.

What is already known about this subject

• Deficit in central cholinergic neurotransmission is a consistent change associated with Alzheimer''s disease (AD).
• Donepezil hydrochloride exhibits selective inhibition of acetylcholinesterase (AChE) and is widely used for the treatment of AD.
• The biodistribution of donepezil in the brain after administration is not precisely understood in vivo.
• There is no method to measure the amount of binding of orally administered donepezil to AChE.

What this study adds

• This study clearly visualizes the distribution of donepezil in human brain using [¹¹C]-donepezil and positron emission tomography.
• This study demonstrates prominent reduction of the donepezil binding site in the AD brain.
• This study provides methodology to measure the AChE binding occupancy of orally administered donepezil and provides a new surrogate marker for evaluation and prediction of response to donepezil treatment.

     

Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin

AIMS

Antihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H₁ receptor occupancy (H₁RO) in the brain using positron emission tomography (PET). The aim was to measure H₁RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine.

METHODS

Eight healthy male volunteers (mean age ± SD 24.4 ± 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with ¹¹C-doxepin in a crossover study design. Binding potential ratio and H₁ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H₁RO was examined.

RESULTS

H₁RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H₁ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H₁ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001).

CONCLUSION

Oral bepotastine (10 mg), with its relatively low H₁RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• ‘Bepotastine besilate’ is a novel second-generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies.
• However, only a few clinical studies regarding its sedative property are available.
• In addition, histamine H₁ receptor occupancy (H₁RO) of this new antihistamine has never been measured by positron emission tomography (PET).

WHAT THIS STUDY ADDS

• This paper provides the first measurement result of cerebral H₁RO of bepotastine besilate (approximately 15%) as determined by PET.
• This result is in accordance with the clinical classification of bepotastine as a second-generation antihistamine.
• In addition, the relationship between subjective sleepiness and cerebral H₁RO of this second-generation antihistamine is demonstrated for the first time using a placebo-controlled crossover study design.

     

Quantification of allospecific and nonspecific corneal endothelial cell damage after corneal transplantation

Purpose

To investigate the effect of host immunity (allospecific) and surgical manipulation (non-allospecific) on corneal endothelial cells (CECs) in corneal transplantation.

Methods

Draining lymph nodes and grafted C57BL/6 corneas were harvested from syngeneic recipients, allograft acceptors, and allograft rejectors (BALB/c) 1, 3, and 8 weeks after transplantation. We analyzed CEC apoptosis using an ex vivo cornea-in-the-cup assay, and visualized cell-to-cell junctions using immunohistochemical staining (ZO-1). Automatic cell analysis using Confoscan software was used to measure CEC density as well as changes in CEC morphology by quantifying the coefficient of variation in cell size (polymegethism) and shape (pleomorphism).

Results

The cornea-in-the-cup assay showed that allogeneic acceptor T cells and to an even greater extent rejector T cells (but not syngeneic T cells) induced CEC apoptosis. CEC density after corneal transplantation was significantly reduced in allogeneic acceptors compared with syngeneic grafts (P<0.001), and CEC density was even further reduced in the allo-rejector group compared with the allo-acceptor group. Allogeneic grafts showed a greater increase in the coefficient of variation in cell size (polymegethism) when compared with syngeneic grafts 1 week after transplantation (P=P<0.001). However, pleomorphism was not significantly different between syngeneic and allo-acceptor grafts, indicating that polymegethism (but not pleomorphism or cell density) is a sensitive indicator of the effect of alloimmunity on CECs.

Conclusions

Our data demonstrate that host alloimmunity rather than surgical manipulation alone is the major cause of CEC damage in corneal transplantation, and such morphologic changes of CECs can be detected before the clinically visible onset of allograft rejection.     

Inhibitory effects of <Emphasis Type="Italic">Rosa gallica</Emphasis> on the digestive enzymes

The 50% aqueous ethanol extracts of petals of Rosa gallica collected in Xinjiang province, China, exhibited potent inhibitory effects against α-amylase and α-glucosidase. As the active principles, seven hydrolysable tannins were isolated from this species for the first time and elucidated by NMR and ESI-TOF-MS analysis. Quantitative analysis by ultra-performance liquid chromatography demonstrated that the contents of these hydrolysable tannins were 3–5% of the dry weight of the petals, and the hydrolysable tannins must be related to the medicinal utilization of this species.     

Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography

Antihistamines often are self-administered at night as over-the-counter (OTC) sleep aids, but their next-day residual sedative effect has never been evaluated using a reliable quantitative method such as positron emission tomography (PET). We performed a double-blind, placebo-controlled, crossover study in which we evaluated the residual effect the next day after nighttime administration of diphenhydramine, a commonly used OTC sleep aid, in terms of brain H? receptor occupancy (H?RO) measured using 11C-doxepin-PET. We also compared the results of diphenhydramine with those of bepotastine, a second-generation antihistamine. Eight healthy adult male subjects underwent PET measurement the morning (11:00) after random oral administration of diphenhydramine (50 mg), bepotastine (10 mg), or placebo the night before (23:00). Binding potential ratios and H?ROs were calculated in different brain regions of interest such as the cingulate gyrus, frontotemporal cortex, and cerebellum. Subjective sleepiness and plasma drug concentration also were measured. Calculation of binding potential ratios revealed significantly lower values for diphenhydramine than for bepotastine or placebo in all regions of interest (P < 0.01). Cortical mean H?RO after diphenhydramine treatment was 44.7% compared with 16.6% for bepotastine treatment (P < 0.01). Subjective sleepiness was not significantly different among the subjects treated with each test drug or the placebo. In conclusion, the next-day residual sedative effect after nighttime administration of the OTC sleep aid diphenhydramine was verified for the first time by direct PET measurement of H?RO. Taking into account the possible hangover effect of OTC antihistamine sleep aids, care needs to be taken during their administration.     

Radiation therapy for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma

Background. The intrahepatic recurrence rate after curative hepatectomy for hepatocellular carcinoma (HCC) is high, and management of recurrence is thus important for long-term survival. The use of radiation therapy has been relatively uncommon in the treatment of recurrent HCC.Methods. Eight patients underwent radiation therapy for recurrent HCC 12–98 months after hepatectomy. Five of them were treated with protons (250MeV; 68.8–84.5Gy), and three were treated with X-rays (6MV; 60 or 70Gy). One patient received radiation therapy twice for another lesion with a 79-month interval. The target tumors were 1.2–4.5cm. All patients also underwent transcatheter arterial embolization or other regional therapy.Results. Although transient ascites was found in three patients after radiation therapy, no patient died as a result of the irradiation. Seven patients died 9 months to 4 years (median 1 year 6 months) after radiation therapy. Re-recurrence was observed in the irradiated liver in two patients (local control 78%). Four patients died of lung metastasis after radiation therapy. The median survival time was 3 years 3 months (range 1 year 1 month to 8 years 6 months) after recurrence.Conclusion. Multimodality therapy is necessary for the management of recurrence. Radiation therapy could be beneficial when other therapies present some difficulty regarding application or are performed incompletely. It must be emphasized that radiation therapy should be considered in addition to other regional therapies for the treatment of recurrent or re-recurrent HCC, and that radiation therapy can be repeated in selected patients.