Infection in diabetic osteoarthropathy: use of indium-labeled leukocytes for diagnosis

Indium-111 labeled leukocyte imaging was compared with three-phase skeletal scintigraphy as a means of determining whether osteomyelitis was complicating diabetic osteoarthropathy. Three-phase scintigraphy demonstrated increased activity in both infected and noninfected osteopathic bone, with a sensitivity of 75% and a specificity of 56% for osteomyelitis. Leukocyte imaging had the same sensitivity but was most helpful for excluding infection (specificity, 89%) when three-phase imaging could not. Abnormal leukocyte localization was seen at the primary site of infection in all cases within 4 hours after injection. Disadvantages of leukocyte imaging included long preparation time, low count rates resulting in poor spatial resolution, and absence of bone landmarks, which made it difficult to differentiate soft tissue from bone infection.     

Novel electrophilic synthesis of 6-[¹⁸F]fluorodopamine and comprehensive biological evaluation

Purpose

6-[¹⁸F]Fluorodopamine (4-(2-aminoethyl)-5-[¹⁸F]fluorobenzene-1,2-diol, 6-[¹⁸F]FDA) is a tracer for imaging sympathetically innervated tissues. Previous electrophilic labelling methods produced 6-[¹⁸F]FDA with low specific radioactivity (SA) which has limited its wider use. Our aim was to employ electrophilic labelling and increase the SA to around 15?GBq/μmol. We also sought to determine an extensive biodistribution pattern for 6-[¹⁸F]FDA in rats in order to thoroughly identify tissues with dense sympathetic innervation that were specifically labelled with 6-[¹⁸F]FDA. In addition, to investigate the safety profile of 6-[¹⁸F]FDA in larger animals, we performed in vivo studies in pigs.

Methods

6-[¹⁸F]FDA was synthesised using high SA electrophilic [¹⁸F]F₂ as the labelling reagent. Biodistribution and metabolism of 6-[¹⁸F]FDA was determined ex vivo in rats, and in vivo studies were done in pigs.

Results

6-[¹⁸F]FDA was synthesised with 2.6?±?1.1% radiochemical yield. The total amount of purified 6-[¹⁸F]FDA was 663?±?291?MBq at the end of synthesis (EOS). SA, decay corrected to EOS, was 13.2?±?2.7?GBq/μmol. Radiochemical purity exceeded 99.0%. Specific uptake of 6-[¹⁸F]FDA was demonstrated in heart, lung, pancreas, adrenal gland, lower large intestine (LLI), eye, thyroid gland, spleen and stomach tissue. 6-[¹⁸F]FDA in rat plasma declined rapidly, with a half-life of 2?min, indicating fast metabolism. In vivo PET studies in pigs confirmed the tracer could be used safely without pharmacological effects.

Conclusion

6-[¹⁸F]FDA was synthesised with good radiopharmaceutical quality and yields high enough for several human PET studies. The SA of 6-[¹⁸F]FDA was improved by 50- to 500-fold compared to previous electrophilic methods. Uptake of 6-[¹⁸F]FDA was specific in various peripheral organs, indicating that 6-[¹⁸F]FDA PET can be used to investigate sympathoneural functions beyond cardiac studies when higher specific uptake is achieved.     

Dynorphin A-containing neural elements in the nucleus of the solitary tract of the rat. Light and electron microscopic immunohistochemistry

Distribution of dynorphin A (DyA) immunoreactivity in the nucleus of the solitary tract (NTS) was examined in rats after various surgical transections by light and electron microscopic immunohistochemistry. In colchicine-treated animals DyA immunostained were seen in each subdivision of the NTS. In intact rats, dense network of immunopositive nerve fibers was localized light microscopically, and synaptic contacts were found between DyA immunopositive structures (axo-axonic, axo-dendritic synapses), electron microscopicaly. Surgical transections medial, caudal or rostral to the nucleus did not alter the distribution pattern of DyA in the NTS. Lesion immediately lateral to the nucleus resulted in an ipsilateral appearance of immunostained cell bodies. Vagal and glossopharyngeal aferents (including baroreceptor fibers) terminate in the medial and commissural subnucleus of the NTS. Two days after extracranial vagotomy, synaptic contacts between degenerated presynaptic boutons and DyA immunopositive postsynaptic elements were observed in both medial and commissural part of the NTS. These observations provide morphological evidence suggesting that (1) axons of dynorphin A-containing cell bodies form an intrinsic network inside the nucleus; (2) these DyA cells receive direct peripheral inputs through the vagus nerve, and (3) projecting DyA neurons may exist in the NTS, they may innervate medullary, rather than forebrain, higher brainstem or spinal cord neurons.     

Plateletpheresis for postsplenectomy rebound thrombocytosis in a patient with chronic immune thrombocytopenic purpura on romiplostim

Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which IgG‐coated platelets are removed from circulation by the spleen, and platelet production is impaired due to increased thrombopoietin (TPO) clearance. Romiplostim, a novel TPO‐mimetic agent, is approved for patients with ITP that are unresponsive to traditional treatments. However, there is little experience when using this drug before splenectomy. We describe herein the case of a young female with chronic ITP who was treated with romiplostim, underwent splenectomy shortly thereafter, and required plateletpheresis for postoperative rebound thrombocytosis with concomitant neurologic symptoms. J. Clin. Apheresis 28:321–324, 2013. © 2013 Wiley Periodicals, Inc.     

Advanced precancerous lesions within the GI tract: The molecular background

The mainstream carcinogenic processes involved within the gastrointestinal tract are characterized by phenotypic multistep progression cascades that eventually result in full-blown cancers. In this scenario, the understanding of the molecular dysregulations underlying the precancerous lesions is increasing but still remains incomplete. However, in recent years, the enthusiastic rise of innovative technologies (i.e., next-generation sequencing, high-throughput microarray analysis, mass spectrometry based proteomics) and the unexpected discovery of new classes of biomarkers (i.e., miRNA, long-noncoding RNAs) prompted new strength in the exploration of the accurate and comprehensive molecular characterization of premalignant and malignant neoplastic lesions. The challenge ahead lies in the reliable identification of disease progression-specific targets to enable molecular testing in the clinical management of the secondary prevention of gastrointestinal cancers.