Quantification of rate constants for successive enzymatic reactions with DNP hyperpolarized MR.

A kinetic model is provided to obtain reaction rate constants in successive enzymatic reactions that are monitored using NMR spectroscopy and hyperpolarized substrates. The model was applied for simulation and analysis of the successive oxidation of choline to betaine aldehyde, and further to betaine, by the enzyme choline oxidase. This enzymatic reaction was investigated under two different sets of conditions: two different choline molecular probes were used, [1,1,2,2-D4 , 1-(13) C]choline chloride and [1,1,2,2-D4 , 2-(13) C]choline chloride, in different MR systems (clinical scanner and high-resolution spectrometer), as well as in different reactors and reaction volumes (4.8 and 0.7 mL). The kinetic analysis according to the model yielded similar results in both set-ups, supporting the robustness of the model. This was achieved despite the complex and negating influences of reaction kinetics and polarization decay, and in the presence of uncontrolled mixing characteristics, which may introduce uncertainties in both effective timing and effective pulses. The ability to quantify rate constants using hyperpolarized MR in the first seconds of consecutive enzyme activity is important for further development of the utilization of dynamic nuclear polarization-MR for biological determinations.

Frequent misdiagnosis of adult polyglucosan body disease.

Adult polyglucosan body disease (APBD) is a rare glycogenosis manifesting progressive spastic paraparesis, sensorimotor polyneuropathy and neurogenic bladder. Misdiagnosis of APBD may lead to unnecessary investigations and to potentially harmful therapeutic interventions. To examine the frequency of misdiagnosis of APBD, we retrospectively reviewed the clinical data of 30 patients diagnosed between 1991 and 2013. Diagnosis was based on the combination of typical clinical and imaging findings, reduced glycogen branching enzyme activity, and the presence of p.Y326S GBE1 mutation. Initial symptoms started in the 5th-6th decade with bladder dysfunction (47 %), gait problems (33 %) or both. Diagnosis of APBD was delayed by 6.8 (±4.8) years. Consistent signs at diagnosis were spasticity in the legs (93 %), decreased or absent ankle reflexes (100 %), bilateral extensor plantar response (100 %) and distal sensory deficit (80 %). Nerve conduction study showed invariable sensorimotor polyneuropathy, and MRI demonstrated cervical spinal cord atrophy (100 %) and leukoencephalopathy (97 %). All 30 patients were initially misdiagnosed. Common misdiagnoses included cerebral small vessel disease (27 %), multiple sclerosis (17 %), amyotrophic lateral sclerosis (17 %) and peripheral neuropathies (20 %). Consequently, 27 % received inappropriate therapy. In addition, lower urinary tract symptoms in 60 % of men were attributed solely to prostatic disorders but did not respond to medical treatment or prostatectomy. These findings suggest that despite limited clinical variability, APBD is invariably misdiagnosed and patients are often mistreated. Physicians' unfamiliarity with the typical clinical and imaging features of APBD appears as the main reason for misdiagnosis.

Pharyngo-occipital artery variant arising proximal to occluded internal carotid artery: the risk of an unnecessary endarterectomy.

Collateral branches originating from the cervical internal carotid artery (ICA) are rare but can have significant clinical and surgical implications. We present a case of pharyngo-occipital artery arising proximal from an occluded ICA that was missed and confused for severe stenosis of the ICA, leading to the misguided indication for carotid endarterectomy. Advanced preoperative studies allowed timely recognition of this anomaly and reconsideration of the therapeutic plan. We stress the importance of recognizing these variants by careful examination of multimodal pre-surgical exams. Awareness of these variants will allow a more precise diagnosis, and more appropriate management of patients with carotid artery disease.

Inadvertent subclavian artery cannulation treated by percutaneous closure.

Accidental arterial puncture occurs in around 1% and 2.7% of jugular and subclavian approaches, respectively. When a line has been inadvertently inserted into an artery at a noncompressible site, there is an increased risk for serious complications. This complication can be treated by either surgical or endovascular intervention or a combination; however, in critically ill patients or in those with impaired coagulation, therapeutic options are more limited. We describe successful endovascular management of inadvertent subclavian artery cannulation during insertion of a triple lumen central line catheter in a 35-year-old man suffering from leukemia, with sepsis and multi-organ failure. He was hypotensive and hemodynamically unstable, with severe coagulopathy. The catheter had entered the artery at the level of the origin of the internal mammary artery, just above the origin of the vertebral artery. The tip was lying in the aortic arch. The artery was successfully closed by endovascular deployment of an 8 French Angio-Seal device (St. Jude Medical, St. Paul, MN, USA). The device is licensed for use in femoral arterial puncture sites but provided safe and effective closure of the subclavian artery puncture in our patient.