Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA) for the treatment of acute ischaemic stroke.

BACKGROUND: The objective of this study was to characterize the comorbidities in a population of patients with an acute ischaemic stroke, comparing patients that received recombinant tissue plasminogen activator (rt-PA) to those that did not receive rt-PA. METHOD: In a retrospective sample of 663 patients admitted for acute ischaemic stroke, this study analysed the effects of co-morbid conditions in the use of rt-PA. It determined non-cerebrovascular risk factors (comorbidities) that differentiate patients who received rt-PA from those who did not receive rt-PA. RESULT: Patients with a history of carotid stenosis, CHF and previous strokes are significantly (p < 0.05) associated with high risk of not receiving rt-PA. A significant number of patients with a history of hypertension and smoking received rt-PA (p < 0.05). CONCLUSION: The findings indicate that certain risk factors including carotid stenosis, CHF and previous stroke history impact the treatment of patients with acute ischaemic stroke, specifically the decision to administer rt-PA. Treatment with rt-PA is dependent on stroke severity and onset to treatment time, but the findings suggest that rt-PA use may also depend on patient comorbidities.

Contribution of long-range interactions to the secondary structure of an unfolded globin.

This work explores the effect of long-range tertiary contacts on the distribution of residual secondary structure in the unfolded state of an alpha-helical protein. N-terminal fragments of increasing length, in conjunction with multidimensional nuclear magnetic resonance, were employed. A protein representative of the ubiquitous globin fold was chosen as the model system. We found that, while most of the detectable alpha-helical population in the unfolded ensemble does not depend on the presence of the C-terminal region (corresponding to the native G and H helices), specific N-to-C long-range contacts between the H and A-B-C regions enhance the helical secondary structure content of the N terminus (A-B-C regions). The simple approach introduced here, based on the evaluation of N-terminal polypeptide fragments of increasing length, is of general applicability to identify the influence of long-range interactions in unfolded proteins.

Femtosecond pulse shaping directly in the mid-IR using acousto-optic modulation.

Pulse shaping directly in the mid-IR is accomplished by using a germanium acousto-optic modulator (Ge AOM) capable of programmable phase and amplitude modulation for IR light between 2 and 18 microm. Shaped waveforms centered at 4.9 microm are demonstrated in both the frequency and the time domains. With a 50% throughput efficiency, the Ge AOM can generate much more intense pulses with higher resolution than can indirect shaping methods. Furthermore, the phase stability of the shaped pulse proved sufficient for cross correlation with unshaped mid-IR pulses. Thus, phase- and amplitude-tailored pulses can now be readily incorporated into phase-sensitive experiments, such as heterodyned 2D IR spectroscopy.

Heterodyned fifth-order two-dimensional IR spectroscopy: third-quantum states and polarization selectivity.

A heterodyned fifth-order two-dimensional (2D) IR spectrum of a model coupled oscillator system, Ir(CO)(2)(C(5)H(7)O(2)), is reported. The spectrum is generated by a pulse sequence that probes the eigenstate energies up to the second overtone and combination bands, providing a more rigorous potential-energy surface of the coupled carbonyl local modes than can be obtained with third-order spectroscopy. Furthermore, the pulse sequence is designed to generate and then rephase a two-quantum coherence so that the spectrum is line narrowed and the resolution improved for inhomogeneously broadened systems. Features arising from coherence transfer processes are identified, which are more pronounced than in third-order 2D IR spectroscopy because the transition dipoles of the second overtone and combination states are not rigorously orthogonal, relaxing the polarization constraints on the signal intensity for these features. The spectrum provides a stringent test of cascading signals caused by third-order emitted fields and no cascading is observed. In the Appendix, formulas for calculating the signal intensities for resonant fifth-order spectroscopies with arbitrarily polarized pulses and transition dipoles are reported. These relationships are useful for interpreting and designing polarization conditions to enhance specific spectral features.

Vibrational dynamics of ions in glass from fifth-order two-dimensional infrared spectroscopy.

The vibrational dynamics of the first four antisymmetric stretch vibrational levels of azide in an ionic glass have been measured and correlated using a heterodyned fifth-order two-dimensional infrared pulse sequence. By rephasing a two-quantum coherence, a process not possible with third-order spectroscopy, solvent effects on the frequencies and anharmonicities of the potential energy surface are measured. Fifth-order pulse sequences are another step towards precisely controlling vibrational coherence in analogy to the manipulation of spins in NMR but with ultrafast time resolution.

Heterodyned fifth-order 2D-IR spectroscopy of the azide ion in an ionic glass.

A heterodyned fifth-order infrared pulse sequence has been used to measure a two-dimensional infrared (2D-IR) spectrum of azide in the ionic glass 3KNO3:2Ca(NO3)2. By rephasing a two-quantum coherence, a process not possible with third-order spectroscopy, the 2D-IR spectra are line narrowed, allowing the frequencies, anharmonicities, and their correlations to be measured for the first four (nu=0-3) antisymmetric stretch vibrational levels. In this glass, the vibrational levels are extremely inhomogeneously broadened. Furthermore, the glass shifts the energy of the nu=3 state more than the others, causing an inhomogeneous distribution in the anharmonic constants that are partially correlated to the inhomogeneous distribution of the fundamental frequency. These effects are discussed in light of the strong interactions that exist between the charged solute and solvent. Since this is the first example of a heterodyned fifth-order infrared pulse sequence, possible cascaded contributions to the signal are investigated. No evidence of cascaded signals is found. Compared to third-order spectroscopies, fifth-order pulse sequences provide advanced control over vibrational coherence and population times that promise to extend the capabilities of ultrafast infrared spectroscopy.

A pulse sequence for directly measuring the anharmonicities of coupled vibrations: Two-quantum two-dimensional infrared spectroscopy.

We have experimentally demonstrated a pulse sequence for the acquisition of heterodyned two-dimensional infrared (2D IR) spectra that correlates the overtone and combination bands to the fundamental frequencies. The spectra are generated by Fourier transforming the time domain signal that is allowed to evolve during one- and two-quantum coherence times. In this manner, the overtone and combination bands appear along the two-quantum axis, resulting in a direct determination of the diagonal and off-diagonal anharmonicities. To demonstrate this pulse sequence, we have collected two-quantum 2D IR spectra of a ruthenium dicarbonyl complex, extracted the diagonal and off-diagonal anharmonicities, and simulated the spectra using an exciton model. Several polarization conditions are presented that suppress the diagonal or cross peaks and we have used them to improve the accuracy of the measurement.

Site-specific vibrational dynamics of the CD3zeta membrane peptide using heterodyned two-dimensional infrared photon echo spectroscopy.

Heterodyned two-dimensional infrared (2D IR) spectroscopy has been used to study the amide I vibrational dynamics of a 27-residue peptide in lipid vesicles that encompasses the transmembrane domain of the T-cell receptor CD3zeta. Using 1-(13)C[Double Bond](18)O isotope labeling, the amide I mode of the 49-Leucine residue was spectroscopically isolated and the homogeneous and inhomogeneous linewidths of this mode were measured by fitting the 2D IR spectrum collected with a photon echo pulse sequence. The pure dephasing and inhomogeneous linewidths are 2 and 32 cm(-1), respectively. The population relaxation time of the amide I band was measured with a transient grating, and it contributes 9 cm(-1) to the linewidth. Comparison of the 49-Leucine amide I mode and the amide I band of the entire CD3zeta peptide reveals that the vibrational dynamics are not uniform along the length of the peptide. Possible origins for the large amount of inhomogeneity present at the 49-Leucine site are discussed.