Impact of Hydroxyurea Starting Dose on Pain Outcomes in Patients with Sickle Cell Disease.

In patients with sickle cell disease, hydroxyurea decreases the number of pain crises experienced. This study aimed to evaluate the difference in pain outcomes between patients started on a guideline concordant, weight-based starting dose of at least 15 mg/kg/day of hydroxyurea and those not. The first prescription of hydroxyurea was the baseline date, follow-up was a visit 60-120 days after baseline. The primary outcome was the change in opioid prescribing between baseline and follow-up. 138 patients met inclusion criteria; of these, 55 were started on a guideline concordant dose of hydroxyurea. Greater white blood cell count (9.5 vs 12.0; p < 0.01) was statistically associated with subtherapeutic dosing. Greater actual body weight (68.0 vs 72.1 kg; p = 0.16) also appeared higher in the non-guideline concordant group. No statistically significant difference in opioid prescribing was observed between those started on a guideline concordant dose of hydroxyurea and those who were not. In the guideline concordant starting dose group, 42% had a reduction in pain scores at first follow up, compared to 35% with a non-guideline recommended starting dose. (p = 0.41). While this difference is in the direction that would be expected based on the guidelines, the difference does not appear to be clinically meaningful.

Decoupling of stretch reflex and background muscle activity during anticipatory postural adjustments in humans.

We studied the evolution of stretch reflexes in relation to background electromyographic (EMG) activity in the soleus muscle preceding the onset of voluntary arm raise movements. Our objective was to investigate if changes in reflex EMG and muscle activity occur simultaneously and are similarly scaled in amplitude. Ten human subjects stood with each foot on pedals able to exert short dorsiflexor pulses during stance. Subjects were asked to product consistent voluntary arm raise movements to a target upon a visual cue. In (1/4) of trials, no pulse perturbations were given, but in the remaining (3/4)'s of all trials pulses were given randomly during a 600-ms period, from 400 ms before until 200 ms after the onset of the movements. Perturbation trials were sorted into 20-ms bins post hoc, and the amplitude of the reflex EMG component was calculated and compared to the EMG activity obtained when no pulses were given. Results showed that despite exhibiting similar profiles over time, the background EMG consistently inhibited before the reflex EMG did. However, times of reactivation (rebound) were variable across subjects, with background EMG activating before reflex for some subjects and vice versa for others. The minimum values of inhibition, time of inhibition and time of rebound for background and reflex EMG measures did not show significant linear correlations when all subjects' data were considered. These results suggest that reflex and background EMG components of anticipatory postural adjustments evolve differently in time and amplitude. This has implications for the independent control of reflexes and voluntary muscle activity.

Exploring the human grip force system: a preliminary study.

It has been postulated that cutaneo-receptors from the digits contribute to the control of manipulatory functions of the hand. However, few studies have examined the dynamics of the human grip force system (HGFS) in terms of the dynamic relationship between the vertical loads, taken as an input and the resulting grip force, taken as the output. This paper describes the experimental procedures we have developed to explore the HGFS and presents some initial experimental results. These demonstrate that the step response of the HGFS is biphasic. The first, short latency phase, likely involves only passive and intrinsic components. The second, longer latency phase is likely related to reflex mechanisms since it is preceded by a strong burst of EMG. Moreover, the HGFS response depended nonlinearly on the amplitude and direction of the load applied. These results indicate that further investigation of HGFS dynamics will require the use of nonlinear identification methods.

Methyl Tin(IV) derivatives of HOTeF(5) and HN(SO(2)CF(3))(2): a solution multinuclear NMR study and the X-ray crystal structures of (CH(3))(2)SnCl(OTeF(5)) and [(CH(3))(3)Sn(H(2)O)(2)][N(SO(2)CF(3))(2)].

The new tin(IV) species (CH(3))(2)SnCl(OTeF(5)) was prepared via either the solvolysis of (CH(3))(3)SnCl in HOTeF(5) or the reaction of (CH(3))(3)SnCl with ClOTeF(5). It was characterized by NMR and vibrational spectroscopy, mass spectrometry, and single crystal X-ray diffraction. (CH(3))(2)SnCl(OTeF(5)) crystallizes in the monoclinic space group P2(1)/n (a = 5.8204(8) A, b =10.782(1) A, c =15.493(2) A, beta = 91.958(2) degrees, V = 971.7(2) A(3), Z = 4). NMR spectroscopy of (CH(3))(3)SnX, prepared from excess Sn(CH(3))(4) and HX (X = OTeF(5) or N(SO(2)CF(3))(2)), revealed a tetracoordinate tin environment using (CH(3))(3)SnX as a neat liquid or in dichloromethane-d(2) (CD(2)Cl(2)) solutions. In acetone-d(6) and acetonitrile-d(3) (CD(3)CN) solutions, the tin atom in (CH(3))(3)SnOTeF(5) was found to extend its coordination number to five by adding one solvent molecule. In the strong donor solvent DMSO, the Sn-OTeF(5) bond is broken and the (CH(3))(3)Sn(O=S(CH(3))(2))(2)(+) cation and the OTeF(5)(-) anion are formed. (CH(3))(3)SnOTeF(5) and (CH(3))(3)SnN(SO(2)CF(3))(2) react differently with water. While the Te-F bonds in the OTeF(5) group of (CH(3))(3)SnOTeF(5) undergo complete hydrolysis that results in the formation of [(CH(3))(3)Sn(H(2)O)(2)](2)SiF(6), (CH(3))(3)SnN(SO(2)CF(3))(2) forms the stable hydrate salt [(CH(3))(3)Sn(H(2)O)(2)][N(SO(2)CF(3))(2)]. This salt crystallizes in the monoclinic space group P2(1)/c (a = 7.3072(1) A, b =13.4649(2) A, c =16.821(2) A, beta = 98.705(1) degrees, V = 1636.00(3) A(3), Z = 4) and was also characterized by NMR and vibrational spectroscopy.

Synthesis and characterization of the SO(2)N(3)(-), (SO(2))(2)N(3)(-), and SO(3)N(3)(-) anions.

SO(2) solutions of azide anions are bright yellow, and their Raman spectra indicate the presence of covalently bound azide. Removal of the solvent at -64 degrees C from CsN(3) or N(CH(3))(4)N(3) solutions produces yellow (SO(2))(2)N(3)(-) salts. Above -64 degrees C, these salts lose 1 mol of SO(2), resulting in white SO(2)N(3)(-) salts that are marginally stable at room temperature and thermally decompose to the corresponding azides and SO(2). These anions were characterized by vibrational and (14)N NMR spectroscopy and theoretical calculations. Slow loss of the solvent by diffusion through the walls of a sealed Teflon tube containing a sample of CsSO(2)N(3) in SO(2) resulted in white and yellowish single crystals that were identified by X-ray diffraction as CsSO(2)N(3).CsSO(3)N(3) with a = 9.542(2) A, b = 6.2189(14) A, c = 10.342(2) A, and beta = 114.958(4) degrees in the monoclinic space group P2(1)/m, Z = 2, and Cs(2)S(2)O(5).Cs(2)S(2)O(7).SO(2), respectively. Pure CsSO(3)N(3) was also prepared and characterized by vibrational spectroscopy. The S-N bond in SO(2)N(3)(-) is much weaker than that in SO(3)N(3)(-), resulting in decreased thermal stability, an increase in the S-N bond distance by 0.23 A, and an increased tendency to undergo rotational disorder. This marked difference is due to SO(3) being a much stronger Lewis acid (pF(-) value of 7.83) than SO(2) (pF(-) value of 3.99), thus forming a stronger S-N bond with the Lewis base N(3)(-). The geometry of the free gaseous SO(2)N(3)(-) anion was calculated at the RHF, MP2, B3LYP, and CCSD(T) levels. The results show that only the correlated methods correctly reproduce the experimentally observed orientation of the SO(2) group.