Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.

OBJECTIVES: We tested whether improvements in depressive symptoms precede improved adherence to aspirin in patients with acute coronary syndromes (ACS). BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence. METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed. RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect -0.32, p = 0.016). CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.     

Changes in the human vocal tract due to aging and the acoustic correlates of speech production: a pilot study.

This investigation used a derivation of acoustic reflection (AR) technology to make cross-sectional measurements of changes due to aging in the oral and pharyngeal lumina of male and female speakers. The purpose of the study was to establish preliminary normative data for such changes and to obtain acoustic measurements of changes due to aging in the formant frequencies of selected spoken vowels and their long-term average spectra (LTAS) analysis. Thirty-eight young men and women and 38 elderly men and women were involved in the study. The oral and pharyngeal lumina of the participants were measured with AR technology, and their formant frequencies were analyzed using the Kay Elemetrics Computerized Speech Lab. The findings have delineated specific and similar patterns of aging changes in human vocal tract configurations in speakers of both genders. Namely, the oral cavity length and volume of elderly speakers increased significantly compared to their young cohorts. The total vocal tract volume of elderly speakers also showed a significant increment, whereas the total vocal tract length of elderly speakers did not differ significantly from their young cohorts. Elderly speakers of both genders also showed similar patterns of acoustic changes of speech production, that is, consistent lowering of formant frequencies (especially F1) across selected vowel productions. Although new research models are still needed to succinctly account for the speech acoustic changes of the elderly, especially for their specific patterns of human vocal tract dimensional changes, this study has innovatively applied the noninvasive and cost-effective AR technology to monitor age-related human oral and pharyngeal lumina changes that have direct consequences for speech production.     

Cine CT for attenuation correction in cardiac PET/CT.

In dual-modality PET/CT systems, the CT scan provides the attenuation map for PET attenuation correction. The current clinical practice of obtaining a single helical CT scan provides only a snapshot of the respiratory cycle, whereas PET occurs over multiple respiratory cycles. Misalignment of the attenuation map and emission image because of respiratory motion causes errors in the attenuation correction factors and artifacts in the attenuation-corrected PET image. To rectify this problem, we evaluated the use of cine CT, which acquires multiple low-dose CT images during a respiratory cycle. We evaluated the average and the intensity-maximum image of cine CT for cardiac PET attenuation correction. METHODS: Cine CT data and cardiac PET data were acquired from a cardiac phantom and from multiple patient studies. The conventional helical CT, cine CT, and PET data of an axially translating phantom were evaluated with and without respiratory motion. For the patient studies, we acquired 2 cine CT studies for each PET acquisition in a rest-stress (13)N-ammonia protocol. Three readers visually evaluated the alignment of 74 attenuation image sets versus the corresponding emission image and determined whether the alignment provided acceptable or unacceptable attenuation-corrected PET images. RESULTS: In the phantom study, the attenuation correction from helical CT caused a major artifactual defect in the lateral wall on the PET image. The attenuation correction from the average and from the intensity-maximum cine CT images reduced the defect by 20% and 60%, respectively. In the patient studies, 77% of the cases using the average of the cine CT images had acceptable alignment and 88% of the cases using the intensity maximum of the cine CT images had acceptable alignment. CONCLUSION: Cine CT offers an alternative to helical CT for compensating for respiratory motion in the attenuation correction of cardiac PET studies. Phantom studies suggest that the average and the intensity maximum of the cine CT images can reduce potential respiration-induced misalignment errors in attenuation correction. Patient studies reveal that cine CT provides acceptable alignment in most cases and suggest that the intensity-maximum cine image offers a more robust alternative to the average cine image.     

Chronic Ethanol Inhibits Inositol Metabolism in Specific Brain Regions

Many neurotransmitters and hormones in the nervous system transmit signals through receptors coupled to the poly-phosphoinositide (PI) signaling pathway. In this study, an in vivo protocol with (³H]inositol was used to examine the effect of chronic ethanol administration on inositol metabolism and poly-PI turnover in the cerebral cortex, hippocampus, and cerebellum of mouse brain. C57BL/6 mice were given a nutritionally complete liquid diet containing either ethanol (5%, w/v) or isocaloric sucrose for 2 months. Mice were injected intracerebrally with ^rH]inositol; after 16 or 24 hr, they were injected intraperitoneally with lithium (8 mEq/kg body weight) to inhibit the inositol monophosphatase (IP₁) activity. All mice were decapitated 4 hr after lithium injection. Labeled inositol phospholipids accounted for 16 to 23% of total labeled inositol in different regions of control mouse brain, and the percentages in the hippocampus were consistently higher than the cerebral cortex and cerebellum. In control mice, the percentages of labeled IP, after a 4-hr lithium treatment were 11.5%, 9.9%, and 3.7% for cerebral cortex, hippocampus, and cerebellum, respectively. Chronic ethanol feeding resulted in a significant (p < 0.05) decrease in the percent of labeled IP₁ and inositol phospholipids, and this effect was observed in the cerebral cortex and, to a lesser extent, hippocampus but not cerebellum. When ratios of labeled IP₁ were expressed against labeled inositol phospholipids as an index of the poly-PI turnover activity, significant decreases in IP/lipid ratios were observed in the cerebral cortex, but not the hippocampus or cerebellum. Although mice killed 24 + 4 hr after the last ethanol feeding would have experienced an 8-hr period of ethanol withdrawal, compared with the 16 + 4-hr group, no differences in IP/lipid ratios were observed between the two time groups. These results illustrate regional differences in the effect of chronic ethanol on inositol metabolism in the brain, but no difference in poly-PI turnover in brain due to ethanol withdrawal.     

The pharmacokinetics of isoxicam in elderly patients with rheumatoid arthritis

Nineteen patients, aged 60 years and over, with rheumatoid arthritis participated in a clinical trial to investigate the pharmacokinetics of isoxicam (a new non-steroidal anti-inflammatory drug) in this age group. The purpose of the study was to determine if the pharmacokinetics are different compared to a younger healthy population. The half-lives were independent of dosage, indicating linearity of pharmacokinetics. Furthermore, the half-lives after repeated dosing were not different from those found after single doses of 400 mg. This shows that there is neither undue accumulation of the drug nor induction of its own metabolism. These results are similar to the results obtained in other centres when isoxicam was administered to healthy subjects between 18 and 32 years.     

Chronic exposure to cold stress alters electrophysiological properties of locus coeruleus neurons recorded in vitro.

Chronic stress exposure can alter central noradrenergic function. Previously, we reported that in chronically cold-exposed rats the release of norepinephrine and electrophysiological activation of locus coeruleus (LC) neurons is enhanced in response to multiple excitatory stimuli without alterations in basal activity. In the present studies, we used in vitro intracellular recording techniques to explore the effect of chronic cold exposure on the basal and evoked electrophysiological properties of LC neurons in horizontal slices of the rat brainstem. Consistent with our findings from in vivo experiments, chronic cold exposure did not affect basal firing rate. Furthermore, gross morphology of LC neurons and spike waveform characteristics were similar in slices from control and previously cold-exposed rats. However, excitability in response to intracellular current injection and input resistance were larger in slices from previously cold-exposed rats. In addition, the accommodation of spike firing in response to sustained current injection was smaller and the period of postactivation inhibition appeared to be less in LC neurons from cold-exposed rats. These data demonstrate that the stress-evoked sensitization of LC neurons observed in vivo is at least in part maintained in the slice preparation and suggest that alterations in electrophysiological properties of LC neurons contribute to the chronic stress-induced sensitization of central noradrenergic function observed in vivo. Furthermore, the present data suggest that an alteration in autoinhibitory control of LC activity is involved in the chronic stress-induced alterations. The enhanced functional capacity of LC neurons following cold exposure of rats may represent a unique model to study the mechanisms underlying the alterations in central noradrenergic function observed in humans afflicted with mood and anxiety disorders.