Synthesis,radiosynthesis, and positron emission tomography neuroimaging using 5-[18F]fluoro-L-amino suberate

System xc- (Sx_c-) has emerged as a new biological target for PET studies to detect oxidative and excitotoxic stress. Notably, applications have, thus far, been limited to tumour imaging although Sx_c^-) may play a major role in neurodegeneration. The synthesis procedures of tosylate precursor and its translation to Sx_c- PET tracer 5[18F]fluoro-L-amino suberate by manual and automated radiosyntheses are described. A brain-PET study has been conducted to evaluate the tracer uptake into brain in healthy mice.     

Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency: the case for screening all newborns

Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is the most common inborn error of fatty acid oxidation with a frequency of 1 in 12,000, an estimated four new cases in the state of Oklahoma each year. The first clinical manifestation is a hypoglycemic episode any time between the newborn period to adulthood. Largely due to failure of diagnosis, the first episode can be lethal, with a frequency of early mortality of 25%. We report a child with MCAD deficiency admitted to the OU Medical Center-Children's Hospital to illustrate the molecular basis, clinical features, and management of the disorder and to present the pros and cons of instituting newborn screening in our state. Such screening is already part of routine newborn metabolic screening in four states. In Oklahoma and elsewhere, there is current discussion, which we summarize, on whether or not to include MCAD deficiency in the routine neonatal screening program. We suggest the evidence says, "Start now."     

Disposition and metabolism of [3H] cocaine in acutely and chronically treated monkeys

Monkeys were chronically treated with cocaine, 1 mg/kg subcutaneously twice daily for the first week and four times daily for the subsequent 21 weeks, followed by the same dose of [³H] cocaine injected intravenously. The $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ values of cocaine in the plasma, cerebrospinal fluid, liver, kidney and heart of acutely and chronically treated monkeys were 1.32, 0.85; 0.91, 0.75; 1.60, 1.29; 0.90, 0.91; and 1.02, 0.91 h, respectively. In areas of the central nervous system (CNS) the values for the acute and chronic group ranged between 0.75 – 0.90 and 0.62 – 0.84 h, respectively. With the exception of the temporal cortex, cerebellum and caudate nucleus, the $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ were not significantly different in the two groups. Norcocaine, benzoylnorecgonine, benzoylecgonine, and minor amounts of ecgonine were the metabolites of cocaine in the brain of monkeys. Significant amounts of total radioactivity due to benoylnorecgonine and benzoylecgonine persisted in the CNS of chronically treated monkeys. Norcocaine constituted approximately 3, 21, 8, and 6% of the values of cocaine in the CNS areas in the acutely treated monkeys, and 14, 13, 14, and 16% in the chronically treated ones, 0.25, 0.5, 1 and 2 h after cocaine injection. A biphasic pattern of peak levels in the plasma and bile of chronically treated monkeys indicated enterohepatic circulation of cocaine. Brain to plasma and CSF to plasma ratios of cocaine were higher in the chronic than in the acute group. The amounts of cocaine excreted in urine and feces as a percentage of dose were 0.23 – 5.1 and 0.1 – 0.23 in the acute group, 0.54 – 7.0 and 0.1 – 0.14 in the chronic group. Major excretion of radioactivity occurred in urine within 24 h and the mean values of the total radioactivity in urine and feces (96 h) in the acute and chronic groups were 60.4 and 63.2% of the dose, respectively. Norcocaine, benzoylnorecgonine, benzoylecgonine, ecgonine methyl ester, ecgonine, and unidentified compounds were the urinary metabolites of cocaine in the two groups. The percentage of benzoylecgonine was higher, that of benzoylnorecgonine lower, in the chronic than in the acute group and the values of other metabolites were not markedly different in the two groups. Data support the postulate that chronic treatment of monkeys with cocaine does not produce dispositional tolerance.     

Bilateral Hahn–Steinthal fracture: a case report and review of literature

Capitellar fractures are rare. If anatomy is not reconstructed accurately, elbow function is sub-optimal. Various studies have shown good outcome in Type I Hahn–Steinthal fractures. There is only one report of a bilateral capitellar fracture in the English literature so far. We report another case of the same. A 26-year-old mother slipped and fell on level ground. She sustained closed injury to both her elbows. Radiographs revealed bilateral, displaced Hahn–Steinthal fracture of the capitellum. She underwent open anatomic reduction and stabilisation with two partially threaded 4 mm cancellous screws, inserted from posterior to anterior. At 2 months, both fractures united. At final follow-up, 19 months post-operatively, she had full range of movement of both elbows. Anatomic reduction, stable internal fixation and early mobilisation of Type I Hahn–Steinthal capitellar fracture achieves excellent results.