Cu(I)-assisted click chemistry strategy for conjugation of non-protected cross-bridged macrocyclic chelators to tumour-targeting peptides.

Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry has inherent challenges for copper-labeled radiopharmaceuticals. An azide-modified phosphonate-based cross-bridged macrocyclic chelator was synthesized for click chemistry conjugation with azide-modified Y3-TATE (a somatostatin analogue) on resin, without the need for protecting the chelator. The (64)Cu-labeled bioconjugate shows favourable in vitro and in vivo behaviour.

Endovascular recanalization for chronic symptomatic intracranial vertebral artery total occlusion.

Purpose. The outcome of recanalization in patients with chronic symptomatic intracranial vertebral artery (ICVA) total occlusion is poor. This paper reports the technical feasibility and long-term outcome of ICVA stenting in patients with chronic symptomatic total occlusion.

Intra-arterial revascularisation therapy for acute ischaemic stroke: initial experience in a Hong Kong hospital.

Objectives: To assess the outcome of acute ischaemic stroke patients who received intra-arterial therapy in our unit.

Design: Case series.

Setting: A tertiary hospital in Hong Kong.

Angiographic features, collaterals, and infarct topography of symptomatic occlusive radiation vasculopathy: a case-referent study.

Background And Purpose: Occlusive radiation vasculopathy (ORV) predisposes head-and-neck cancer survivors to ischemic strokes.

Methods: We analyzed the digital subtraction angiography acquired in 96 patients who had first-ever transient ischemic attack or ischemic strokes attributed to ORV. Another age-matched 115 patients who had no radiotherapy but symptomatic high-grade (>70%) carotid stenoses were enrolled as referent subjects.

Young ischaemic stroke in South Auckland: a hospital-based study.

Background And Purpose: To analyse the risk factors, trends in incidence and aetiology of stroke in young adults in a hospital-based population in South Auckland, New Zealand.

Method: A retrospective review of patients aged 15 years to 45 years with a discharge diagnosis of ischaemic stroke (ICD 10 Codes I63 - I65, G46, I672, I675-I679, I694- I694) from June 1 2004 to December 31, 2009. Vascular risk factors, demographic factors, stroke severity, stroke subtype, results of investigations and stroke outcome were determined from review of the hospital record (paper copy and electronic record).

Intravenous alteplase for Chinese patients with stroke and borderline eligibility.

Lack of efficacy and safety data among Chinese patients with stroke have contributed to the slow development of stroke thrombolysis as standard-of-care for these patients. We examined a retrospective cohort of 57 patients who received intravenous alteplase for acute ischemic stroke to identify predictors of outcome, including age, stroke severity, onset-to-treatment time, and early ischemic changes on brain CT scan. Overall, the mean National Institute of Health Stroke Scale (NIHSS) score was 15.

Significance of good collateral compensation in symptomatic intracranial atherosclerosis.

Background: Collateral circulation stabilizes cerebral blood flow in patients with acute occlusion, but its prognostic role is less studied in intracranial atherosclerosis and appears different in moderate to severe stenosis. We aimed to study the associations between antegrade flow across stenosis, collateral flow via leptomeningeal anastomosis, and the neurological outcome and recurrence risk in patients with symptomatic intracranial stenosis.

Methods: We examined a cohort of consecutive patients admitted for stroke or transient ischemic attack (TIA) with symptomatic intracranial stenosis confirmed by digital subtraction angiography in a single-center retrospective study.

Is stroke thrombolysis safe and efficacious in Hong Kong?

Objective: To investigate the safety and efficacy of stroke thrombolysis in a local hospital.

Design: Historical cohort study.

Setting: A tertiary hospital in Hong Kong.

Synthesis, Cu(II) complexation, 64Cu-labeling and biological evaluation of cross-bridged cyclam chelators with phosphonate pendant arms.

A new class of cross-bridged cyclam-based macrocycles featuring phosphonate pendant groups has been developed. 1,4,8,11-tetraazacyclotetradecane-1,8-di(methanephosphonic acid) (CB-TE2P, 1) and 1,4,8,11-tetraazacyclotetradecane-1-(methanephosphonic acid)-8-(methanecarboxylic acid) (CB-TE1A1P, 2) have been synthesized and have been shown to readily form neutral copper(II) complexes at room temperature as the corresponding dianions. Both complexes showed high kinetic inertness to demetallation and crystal structures confirmed complete encapsulation of copper(II) ion within each macrocycle's cleft-like structure.

Isomeric trimethylene and ethylene pendant-armed cross-bridged tetraazamacrocycles and in vitro/in vivo comparisions of their copper(II) complexes.

Ethylene cross-bridged tetraamine macrocycles are useful chelators in coordination, catalytic, medicinal, and radiopharmaceutical chemistry. Springborg and co-workers developed trimethylene cross-bridged analogues, although their pendant-armed derivatives received little attention. We report here the synthesis of a bis-carboxymethyl pendant-armed cyclen with a trimethylene cross-bridge (C3B-DO2A) and its isomeric ethylene-cross-bridged homocyclen ligand (CB-TR2A) as well as their copper(II) complexes.

A new phosphonate pendant-armed cross-bridged tetraamine chelator accelerates copper(ii) binding for radiopharmaceutical applications.

A phosphonate pendant-armed cross-bridged cyclam chelator has been synthesized, complexed to Cu(ii), radiolabeled with (64)Cu under mild conditions, and its biodistribution studied.

Acute encephalopathy associated with influenza A infection in adults.

We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios > or =3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae.

Lower fractional anisotropy at the anterior body of the normal-appearing corpus callosum in multiple sclerosis versus symptomatic carotid occlusion.

Introduction: Not uncommonly, differentiating multiple sclerosis (MS) from ischemic cerebral vascular disease is difficult based on conventional magnetic resonance imaging (MRI). We aim to determine whether preferential occult injury in the normal-appearing corpus callosum (NACC) is more severe in patients with MS than symptomatic carotid occlusion by comparing fractional anisotropy (FA) from diffusion tensor imaging (DTI).

Methods: Eighteen patients (eight men, ten women; mean age, 38.

The long and short of it: the influence of N-carboxyethyl versusN-carboxymethyl pendant arms on in vitro and in vivo behavior of copper complexes of cross-bridged tetraamine macrocycles.

A cross-bridged cyclam ligand bearing two N-carboxymethyl pendant arms (1) has been found to form a copper(II) complex that exhibits significantly improved biological behavior in recent research towards (64)Cu-based radiopharmaceuticals. Both the kinetic inertness and resistance to reduction of Cu-1 are believed to be relevant to its enhanced performance. To explore the influence of pendant arm length on these properties, new cross-bridged cyclam and cyclen ligands with longer N-carboxyethyl pendant arms, 2 and 4, and their respective copper(II) complexes have been synthesized.

Synthesis, characterization and in vivo studies of Cu(II)-64-labeled cross-bridged tetraazamacrocycle-amide complexes as models of peptide conjugate imaging agents.

Copper-64, a positron emitter suitable for positron emission tomography (PET), demonstrates improved in vivo clearance when chelated by the cross-bridged tetraazamacrocycle CB-TE2A compared to TETA. Good in vivo clearance was also observed for 64Cu-CB-TE2A conjugated to a peptide, which converts one coordinating carboxylate pendant arm to an amide. To better understand the in vivo stability of peptide- conjugated CB-TE2A, cross-bridged monoamides were synthesized.

A man with labile blood pressure.

Ronald Ma and colleagues discuss the differential diagnosis and management of a patient who presented with recurrent episodes of chest discomfort, palpitations, and labile blood pressure.

Stroke caused by small vessel occlusion in a patient taking etoricoxib and thalidomide.

We report a 33-year-old man with seronegative arthritis who had an acute infarct at the left lentiform nucleus while taking etoricoxib and thalidomide regularly. Extensive investigations did not find any evidence of large artery atherosclerosis, vasculitis, cardioembolic source or anti-phospholipid antibodies. While it is possible that a short smoking history, hyperlipidemia, and the use of thalidomide could have contributed to the thrombosis of a small penetrator vessel, we postulated that the prolonged use of etoricoxib is another possible contributing factor.

Tracheobronchial injuries from blunt trauma.

Tracheobronchial injuries from trauma can be life threatening. We present a case report of a 23-year-old man who suffered a left main bronchus transection after a motorbike accident. The diagnostic and management issues surrounding tracheobronchial injuries are reviewed.

Investigation of copper-azamacrocyclic complexes by high-performance liquid chromatography.

The use of copper radioisotopes in imaging and therapy has prompted an increased interest in chelators which form stable copper complexes, such as Cu(II)-azamacrocyclic complexes. The effects of charge, stability and the size of the macrocyclic backbone of the Cu(II)-azamacrocyclic complexes on biological behavior have been evaluated. Here we report a reversed-phase high-performance liquid chromatography (HPLC) method to separate several Cu(II)-azamacrocyclic complexes, including Cu(II) complexes of 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.

Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS.

The cross-bridged tetraamine ligand 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H2CB-TE2A) allows formation of a radio-copper complex with higher in vivo stability than that of the corresponding non-cross-bridged analog 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA).