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A large alkaptonuria (AKU) cohort was studied to better characterise the poorly understood phenotype of aortic stenosis of rare disease AKU.Eighty-one patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Nine only attended once. Fifty-one attended more than once and received nitisinone 2 mg daily. Twenty-one attended at least twice without receiving nitisinone. Assessments included questionnaire analysis, standard transthoracic echocardiography, as well as photographs of ochronotic pigment in eyes and ears at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. The prevalence of aortic stenosis and aortic valve replacement were 22.2 and 6.2% in the current group. Aortic maximum velocity (Vmax) was directly related to varying degrees to age (R = 0.58, p 0.001), systolic blood pressure (R = 0.32, p 0.05), serum homogentisic acid (sHGA) (R = 0.28, p 0.05), ochronosis scores (R = 0.72, p 0.001), and alkaptonuria severity score index (AKUSSI) (R = 0.58, p 0.001) on linear regression analysis. Age and ochronosis scores were significantly related to Vmax on multiple regression analysis (p 0.005). Nitisinone decreased sHGA, 24-h urine HGA (uHGAAortic valve disease is highly prevalent in this NAC cohort, and strongly associated with ochronosis and disease severity. Nitisinone decreases ochronosis and had a similar significant effect on Vmax.

An experimental and theoretical analysis of multiple-quantum (MQ)-like artifacts in 2D NMR spectra of water is presented and discussed. During the t 1 domain, either magnetic field gradients or Q -switching techniques, were used to minimize radiation damping effects. Nevertheless, a myriad of MQ artifacts, in excess of Δm = ± 20, were observed in the indirectly detected t 1 domain. The source of these MQ-like artifacts has been traced, rather surprisingly, to radiation damping in the t 2 domain. This conclusion was reached experimentally, using Q -switching experiments in both the t 1 and t 2 domains, and confirmed theoretically, using a modification of the radiation damping theory of Vlassenbroek et al., J. Chem. Phys. 103 (1995) 5886.

Recently, Warren and co-workers have shown that double quantum, gradient selective, 2D NMR experiments can give rise to apparently unreconcilable double quantum signals and intermolecular cross peaks. These experiments have been used to challenge the basic assumptions of room temperature NMR. We re-examine the gradient-induced multiple spin echo explanation, first discussed by Warren. It is shown that simple analytical explanations can be provided for (i) double quantum peaks, (ii) cross correlation peaks, (iii) the amplitudes of the observed cross peaks, and (iv) the disappearance of the cross peaks when the solvent and solute are placed in different tubes.