Amyloid deposit corresponds to technetium-99m-pyrophosphate accumulation in abdominal fat of patients with transthyretin cardiac amyloidosis.

BACKGROUND: Radionuclide imaging using bone-avid tracers plays a critical role in diagnosing transthyretin cardiac amyloidosis (ATTR-CA), but technetium-99m-pyrophosphate (PYP) rarely allows the detection of extracardiac amyloid infiltration. We retrospectively investigated the frequency of PYP uptake in the subcutaneous abdominal fat of patients with ATTR-CA and its relevance to the results of fine-needle aspiration biopsy (FNAB) of this tissue. METHODS: Chest-centered images of PYP scintigraphy were obtained 2 h after the intravenous injection of the tracer (20 mCi), and the frequency of PYP uptake in the subcutaneous abdominal fat was evaluated. Amyloid deposits of fat smears taken by subcutaneous abdominal fat FNAB were assessed by Congo red staining. RESULTS: Twenty-four patients with ATTR-CA were included. Ten (41.7%) patients showed some PYP uptake in the subcutaneous abdominal fat (positive PYP group), and 14 patients did not (negative PYP group). Amyloid deposits were detected by subcutaneous abdominal fat FNAB in 7/10 patients (70.0%) of the positive PYP group versus 0/14 patients (0%) of the negative PYP group, and the difference was significant. CONCLUSIONS: In patients with ATTR-CA, abnormal PYP uptake in the subcutaneous abdominal fat could reflect the regional amyloid deposition confirmed by FNAB of this tissue.

Premature atrial contractions with multiple patterns of aberrant conduction followed by torsade de pointes in a patient with polymyalgia rheumatica: A case report.

RATIONALE: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited. PATIENT CONCERNS: An 85-year-old Japanese woman with active PMR developed first syncope. DIAGNOSIS: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP. INTERVENTIONS: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective. OUTCOMES: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia. LESSONS: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Variant Angina with Spontaneously Documented Ischemia- and Tachycardia-induced "Lambda" Waves.

In a patient with variant angina of the proximal left anterior descending coronary artery, myocardial ischemia changed the QRS-ST-T configurations without J-waves into those resembling "lambda" waves at maximal ST-segment elevation, and couplets or triplets of supraventricular extrasystole (SVE) changed the ischemia-induced "lambda" waves into QRS-ST-T configurations resembling a "tombstone" morphology or "monophasic QRS-ST complex." At the resolution phase of coronary spasm, the QRS-ST-T configurations returned to those without J-waves and were changed by SVE into "lambda" waves. Interestingly, neither ischemia- nor SVE-induced "lambda" waves or SVE-induced "tombstone" morphology or "monophasic QRS-ST complex" were complicated by ventricular tachyarrhythmia.

Suppression of amiodarone-induced torsade de pointes by landiolol in a patient with atrial fibrillation-mediated cardiomyopathy.

An elderly Japanese woman developed acute decompensated heart failure caused by persistent atrial fibrillation (AF) and left ventricular systolic dysfunction. Approximately 6 days after starting intravenous administration of amiodarone (600 mg/day) for maintaining sinus rhythm after cardioversion of AF, electrocardiograms revealed a prolonged QT interval associated with torsade de pointes (TdP). The amiodarone-induced TdP disappeared after intravenous administration of landiolol plus magnesium and potassium, without discontinuation of amiodarone or overdrive cardiac pacing, although the prolonged QT interval persisted. To the best of our knowledge, this is the first report that landiolol could be effective for amiodarone-induced TdP.

Biomembrane damage caused by exposure to multi-walled carbon nanotubes.

Carbon nanotubes (CNTs) have potential as not only electrical materials but also biomedical devices. However, some findings have been reported indicating that the use of CNTs is accompanied by a risk of the development of certain diseases such as pulmonary fibrosis and pleura mesothelioma; and one of the reasons for this risk may be macrophage cell death. In the present study, to elucidate the mechanism of macrophage cell death by CNTs, we focused on biomembrane damage caused by multi-walled CNTs (MWCNTs). When the distribution of MWCNTs in RAW264 cells was observed under a light microscope, MWCNTs were located on the surface of the plasma membrane; and a portion of them seemed to stick into it. The acute cytotoxicity toward RAW264 cells was examined by performing the LDH cytotoxic test, and LDH release was detected after exposure to 100 µg/ml CNT. To examine the physical damage to biomembranes by CNT exposure, we conducted a calcein release assay using calcein-encapsulated liposomes. The results indicated that an increase in the permeability of the lipid bilayer was induced by MWCNTs. The present study thus demonstrated for the first time that a high concentration of MWCNTs was cytotoxic to macrophages and suggested that the direct physical perturbation of biomembranes by MWCNTs plays a role in this activity.

PET imaging of brain cancer with positron emitter-labeled liposomes.

Since nanocarriers such as liposomes are known to accumulate in tumors of tumor-bearing animals, and those that have entrapped a positron emitter can be used to image a tumor by PET, we applied (18)F-labeled 100-nm-sized liposomes for the imaging of brain tumors. Polyethylene glycol (PEG)-modified liposomes, which are known to accumulate in tumors by passive targeting and those modified with Ala-Pro-Arg-Pro-Gly, which are known to home into angiogenic sites were used. Those liposomes labeled with DiI fluorescence accumulated in a glioma implanted in a rat brain 1h after the injection, although they did not accumulate in the normal brain tissues due to the protection afforded by the blood-brain barrier. Preformed liposomes were easily labeled with 1-[(18)F]fluoro-3,6-dioxatetracosane, and enabled the imaging of gliomas by PET with higher contrast than that obtained with [(18)F]deoxyfluoroglucose. In addition, the smallest tumor among those tested, having a diameter of 1mm was successfully imaged by the liposomal (18)F. Therefore, nanocarrier-based imaging of brain tumors is promising for the diagnosis of brain cancer and possible drug delivery-based therapy.