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Biomedical subjects

E Lin

Publications and source records attributed to E Lin.

At least 37 records · Page 2Linked to original sources

Chronic physical illness, psychiatric disorder and disability in the workplace.

While agreement is growing that mental illness burdens the North American economy, how it impacts productivity--particularly compared to physical illness--is unclear. Hypothesizing that lost work days are only the tip of the iceberg, we also examined the association of mental and chronic physical illness with partial work days and days requiring extra effort to function. Data from 4225 employed individuals, aged 18-54, were analyzed. These were a subset of respondents to the Ontario Health Survey's Mental Health Supplement, a 1990/91 epidemiologic survey of households across Ontario, Canada. Psychiatric disorder was assessed using the University of Michigan' modification of WHO's Composite International Diagnostic Interview (UM-CIDI). Similar to US reports, professional/managerial groups had lower rates of affective and anxiety disorders and fewer disability days compared to the rest of the workforce. However, no single occupational group was consistently at greater risk for either physical or psychiatric problems. Even after accounting for sociodemographic characteristics and work conditions, mental and physical status had clear, but different, impacts on productivity. Physical conditions alone had a fairly constant effect across all types of disability days and were the largest contributor to total work day loss. They also significantly impacted partial and extra effort days but were far less important than conditions involving a mental disorder. Respondents with mental health problems, either alone or in combination with physical illnesses, appeared more likely to go to work but to require greater effort to function. WHO projects that mental illness will become the second most important cause of global disease burden in the next century. Our findings suggest that among working individuals, it affects productivity more subtly than does physical illness. However, with an estimated eight percent of Ontario's workforce experiencing more than two months annually of decreased productivity, it still incurs significant social and economic costs.

Adult↗

Flumazenil reversal of carisoprodol (Soma) intoxication.

A 52-year-old woman presented with central nervous system depression and a Glasgow Coma Score of 9 secondary to ingestion of carisoprodol, a centrally acting muscle relaxant analgesic. After administration of i.v. flumazenil, the patient's neurologic status normalized and she required no further therapy. Carisoprodol and its active sedative-hypnotic metabolite, meprobamate, are gamma aminobutyric acid receptor indirect agonists with central nervous system chloride ion channel conduction effects similar to the benzodiazepines, thus making flumazenil a potentially useful antidote in toxic presentations.

Antidotes↗

Effects of head extension and tongue protrusion on voice perturbation measures.

Head extension with protruded tongue is the position for videolaryngoscopy and simultaneous glottographic recordings including photoglottographic signals. This study investigated the effect of head extension and tongue protrusion on the measures of fundamental frequency, frequency perturbation (jitter), and amplitude perturbation (shimmer). Acoustic signals recorded during sustained vowels were obtained from 49 women and 66 men with no speech or voice disorders in different head-tongue positions. Head extension was associated with increased fundamental frequency and decreased shimmer. In men, head extension did not appear to affect jitter. When the tongue was protruded, head extension tended to lower jitter. For both genders, tongue protrusion was associated with decreased fundamental frequency with head extension. In the men, tongue protrusion tended to increase shimmer when the head was in the neutral position. In the women, tongue protrusion was associated with increased jitter and increased shimmer and was most evident in the head-neutral position. These findings supported a physical linkage hypothesis of the relationship between vocal tract configuration and vocal fold vibration, suggesting that head-tongue position must be taken into account when comparing voice measures.

Adult↗

Effects of simulated source of tremor on acoustic and airflow voice measures.

To test the effects of different sources of tremor on the voice, tremor was simulated by external rhythmic perturbation of structures at the subglottal, glottal, and supraglottal levels in 10 healthy subjects. The acoustic and airflow signals simultaneously recorded during sustained phonation in the normal and the 3 simulated tremor conditions were analyzed and compared. Voice measures included: fundamental frequency, 2 short-term perturbation measures (jitter and shimmer), and 3 long-term tremor measures (prominence ratios of the spectral peaks of the acoustic frequency contour, acoustic amplitude contour, and airflow contour). Measures of fundamental frequency and percent shimmer were not significantly affected by the simulated tremors. Measures of percent jitter and the amplitudes of the long-term frequency and amplitude modulations were most prominently increased when respiratory drive was perturbed by simulated tremor. Spectral analysis of the acoustic amplitude contour was most useful in distinguishing the 3 sites of simulated tremor.

Adolescent↗

Elevation of IL-18 in human sepsis.

Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine that shares biochemical features with IL-1beta and acts in part by inducing interferon-gamma (IFN-gamma). Endotoxic bacterial lipopolysaccharide (LPS) (1 or 2 ng/kg) was insufficient to increase plasma IL-18 in five healthy adults measured 3, 12, and 24 hr following challenge. In contrast, in the first 96 hr of admission to the surgical intensive care unit, mean maximal serum IL-18 was elevated (1,122 +/- 259 pg/ml) in nine septic patients compared to six healthy adults (191 +/- 42 pg/ml), P < 0.01). Serum IL-18 concentrations in septic patients did not correlate with other measured inflammatory mediators: tumor necrosis factor, IL-6, IL-10, or secretory leukocyte protease inhibitor. Therefore, IL-18 circulates in healthy adults and is a component of the human systemic inflammatory response. Further, stimuli other than LPS may induce IL-18 production in vivo in human sepsis.

Adolescent↗

Acoustic and airflow spectral analysis of voice tremor.

Acoustic spectral analysis has been used to describe voice tremor with some success, but no feature distinguishing pathological from normal tremor has been clearly identified. To assist in monitoring voice tremor associated with neurological diseases, objective and quantifiable measures that can distinguish between normal and pathological tremor are desired. This study explored the plausibility of using airflow and acoustic signals to quantify the frequency and amplitude of voice tremor and potentially to distinguish pathological from normal tremor. Subjects were 10 individuals with pathological tremor, most of them individuals with Parkinson's disease, and 10 gender and age-matched individuals with no voice disorder. Simultaneous acoustic and airflow signals were recorded during sustained vowel phonation. The acoustic intensity contours and the airflow signals were submitted to spectral analysis. A peak prominence ratio, defined as the ratio of the spectral peak energy to the overall signal energy, was calculated for each spectral peak below 30 Hz. For each subject, the 6 spectral peaks with the highest peak prominence ratios were selected. Frequency values of the 6 selected acoustic or airflow spectral peaks failed to distinguish tremor group from control group. Peak prominence ratios of the 6 selected acoustic spectral peaks were significantly higher for tremor group than for control group. Although spectral analysis of airflow signals was not useful in differentiating tremor group from control group, acoustic intensity contours and airflow time waveforms were highly and positively correlated in more tremor subjects (90%) than control subjects (40%). This finding suggests that the relationship between acoustic intensity contours and airflow time waveforms may reflect the presence and the source of voice tremor.

Adult↗

Predictors of outcome in a primary care depression trial.

OBJECTIVE: Previous treatment trials have found that approximately one third of depressed patients have persistent symptoms. We examined whether depression severity, comorbid psychiatric illness, and personality factors might play a role in this lack of response. DESIGN: Randomized trial of a stepped collaborative care intervention versus usual care. SETTING: HMO in Seattle, Wash. PATIENTS: Patients with major depression were stratified into severe (N = 149) and mild to moderate depression (N = 79) groups prior to randomization. INTERVENTIONS: A multifaceted intervention targeting patient, physician, and process of care, using collaborative management by a psychiatrist and primary care physician. MEASUREMENTS AND MAIN RESULTS: Patients with more severe depression had a higher risk for panic disorder (odds ratio [OR], 5.8), loneliness (OR, 2.6), and childhood emotional abuse (OR, 2.1). Among those with less severe depression, intervention patients showed significantly improved depression outcomes over time compared with those in usual care (z = -3.06, P<.002); however, this difference was not present in the more severely depressed groups (z = 0.61, NS). Although the group with severe depression showed differences between the intervention and control groups from baseline to 3 months that were similar to the group with less severe depression (during the acute phase of the intervention), these differences disappeared by 6 months. CONCLUSIONS: Initial depression severity, comorbid panic disorder, and other psychosocial vulnerabilities were associated with a decreased response to the collaborative care intervention. Although the intervention was appropriate for patients with moderate depression, individuals with higher levels of depression may require a longer continuation phase of therapy in order to achieve optimal depression outcomes.

Adult↗

Inflammatory cytokines and cell response in surgery.

The systemic inflammatory response as mediated by the cytokine network is undoubtedly complex. While inflammatory cytokines are indispensable in wound healing and the restoration of homeostasis, it is often the excessive activity of either proinflammatory or anti-inflammatory cytokines that causes injury to the host or renders the host immunocompromised, respectively. Central to the functional biology of cytokines in surgical injury and infections are the responses of immune cells to such insults. It is clear that immunocytes are the source of cytokine production, and these products possess important autocrine, as well as systemic activities. The ability to alter immunocyte function through extracellular hormonal influences or by manipulating intracellular signaling mechanisms are potential strategies for regulating the inflammatory cytokine response during injury.

Animals↗

Correlation between glottal area and photoglottographic signal in normal subjects.

Photoglottography (PGG) is an established technique for depicting the vibratory patterns of the vocal folds. The present study investigates the correlation between the glottal area and the corresponding PGG signal. Six normal (five male, one female) subjects who did not use their voices professionally were investigated during constantly sustained phonation at spontaneous pitches. Laryngostroboscopy was performed in combination with PGG. The simultaneously recorded laryngostroboscopic images and PGG signals were directly digitized and stored on a computer. The correlation between the glottal area and the corresponding PGG amplitudes across each vibratory cycle of the vocal folds was calculated and they were found to be highly and positively correlated (r = 0.973, p < 0.001). The PGG signal reflects changes in the glottal area during the vibration cycle of the vocal folds. The proposed simultaneous laryngostroboscopic and PGG technique has proved to be useful for facilitating the interpretation of changes in glottal area.

Adult↗

High-performance liquid chromatographic determination of pyrazinamide in human plasma, bronchoalveolar lavage fluid, and alveolar cells.

A technique is presented for the measurement of pyrazinamide in human plasma, bronchoalveolar lavage, and alveolar cells by reversed-phase column chromatography. The assay utilizes acetazolamide as an internal standard, ultraviolet detection at 268 nm, and an acetonitrile-based mobile phase. Preparation of plasma samples requires a simple deproteinization step, resulting in the development of sharp peaks with retention times of 8.4 and 17 minutes for pyrazinamide and acetazolamide, respectively. Bronchoalveolar lavage and alveolar cell suspensions require an acid extraction with ethyl acetate, evaporation to dryness, and reconstitution. This method provides specific, rapid, and reliable determinations of drug concentrations and therefore is suitable for pharmacological studies, particularly those that are designed to quantitate the intrapulmonary concentrations of pyrazinamide.

Antitubercular Agents↗

Liquid chromatographic determination of rifampin in human plasma, bronchoalveolar lavage fluid, and alveolar cells.

A technique is presented for the measurement of rifampin in humans by reversed-phase column chromatography and postcolumn photo irradiation. The assay employs diazepam as an internal standard and provides specific, rapid, and reliable determinations for drug concentration in plasma, bronchoalveolar lavage (BAL), and alveolar cells (AC). The preparation of plasma and AC samples utilizes a simple deproteinization step, whereas BAL supernatants require a solid-phase extraction. The assay produces sharp peaks with retention times of 6.2 and 15 min for rifampin and diazepam, respectively. The detection limits for rifampin were 0.5 microgram/mL for plasma, 0.015 microgram/mL for BAL supernatants, and 0.03 microgram/mL for AC suspensions. The assay has excellent performance characteristics, making it suitable for pharmacological studies in humans, and it is being used to support a study of the intrapulmonary pharmacokinetics of rifampin.

Anti-Anxiety Agents↗

Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia.

OBJECTIVES: To document changes in serum secretory leukocyte protease inhibitor (SLPI) in human sepsis and in experimental endotoxemia in vivo. To compare changes in serum SLPI in human sepsis with changes in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. To determine whether or not changes in SLPI correlate with the severity of multiple organ dysfunction syndrome as measured by the maximal multiple organ dysfunction score. Finally, because neutrophils have been implicated in tissue injury associated with organ dysfunction, to determine whether recombinant human SLPI blocks activation of isolated human neutrophils. DESIGN: Case-control study and ex-vivo cellular assay. SETTING: Surgical intensive care unit and clinical research center of university hospitals; laboratory of a medical school. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There was a significant dose-dependent elevation (50.2+/-4.0 ng/mL, p = .01) in plasma SLPI 12 hrs after administration of lipopolysaccharide to seven healthy adults (36.4+/-2.3 ng/mL). Further, serum concentrations of SLPI (132+/-15 ng/mL) were elevated in septic surgical patients compared with healthy controls (43+/-2 ng/mL, p < .01) and nonseptic surgical controls (69+/-10 ng/mL, p = .01). Serum SLPI concentrations correlated (r2 = .71, p < .01) better with organ dysfunction as measured by maximal multiple organ dysfunction score than did serum IL-6 (r2 = .49, p < .01), IL-10 (r2 = .05, p = .22), or TNF-alpha (r2 = .02, p = .44). We found that recombinant human SLPI in vitro inhibits TNF-alpha-induced hydrogen peroxide production by human neutrophils (ID50 = 1-2 microg/mL). CONCLUSIONS: Serum SLPI is elevated in human sepsis and experimental endotoxemia. Maximal concentrations of serum SLPI correlate significantly with maximal multiple organ dysfunction scores in patients with sepsis. Secretory leukocyte protease inhibitor may function to limit ongoing neutrophil-mediated tissue injury associated with organ dysfunction.

Adolescent↗

Are there detectable differences in quality of care or outcome of depression across primary care providers?

OBJECTIVE: The objective of this work was to determine whether there are detectable differences among primary care physicians in measures of quality of care or clinical outcome for depressed patients during the first 2 months of treatment with antidepressant medication. METHODS: We studied 1,599 depressed primary care patients initiating antidepressant treatment from 63 family physicians in 4 primary care clinics of a staff-model health maintenance organization. Patients were interviewed 6 to 8 weeks after initiating antidepressant medication with a telephone structured interview that included the Structural Clinical Interview for DSM-IV Diagnoses (SCID). Automated databases of the HMO were used to examine 3 quality-of-care measures: (1) the percentage of patients who had a refill of their antidepressant by 6 weeks, (2) the percentage of patients who had a return visit by 3 weeks, and (3) the percentage of patients having a return visit by 6 weeks. The percentage of patients in each primary care physician panel who had > or =4 persistent DSM-IV depressive symptoms at 6 to 8 weeks was the main clinical outcome variable. To adjust for case-mix differences between physician panels, patient age, gender, and medical comorbidity were controlled for in the analyses. Two covariates were used to adjust for differences in patients' clinical severity: self-report of > or =2 prior depressive episodes and an SCID diagnosis of major depression during the patient's worst episode in the last 2 years. Physician age, gender, and part-time versus full-time practice were also used as covariates. RESULTS: The wide observed range of variability in quality-of-care and clinical outcome measures by physician practice decreased markedly in the statistical model that controlled for patient-level covariates and differences in the number of patients seen per provider. We did not detect differences in physician practice for the percentage of patients who had a return visit by 3 or 6 weeks, the percentage of patients who had a refill of their antidepressant prescription by 6 weeks, or the percentage of patients with an adverse clinical outcome of depression. CONCLUSIONS: We did not find important differences in measures of quality of care or patient outcomes by physician. These results may have implications for the use of physician profiling and other forms of physician report cards.

Adolescent↗

Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo.

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents; however, they also have adverse fetal effects such as constriction of the fetal ductus arteriosus. Recently, selective COX-2 inhibitors have been used in the management of preterm labor in the hope of avoiding fetal complications. However, both COX-1 and -2 are expressed by cells of the ductus arteriosus. We used fetal lambs (0.88 gestation) to assess the ability of selective COX-2 inhibitors celecoxib and NS398 to affect the ductus arteriosus. Both selective COX-2 inhibitors decreased PGE(2) and 6ketoPGF(1alpha) production in vitro; both inhibitors constricted the isolated ductus in vitro. The nonselective COX-1/COX-2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro. We used a prodrug of celecoxib to achieve 1.4 +/- 0.6 microg/ml, mean +/- standard deviation, of the active drug in vivo. This concentration of celecoxib produced both an increase in pressure gradient and resistance across the ductus; celecoxib also decreased fetal plasma concentrations of PGE(2) and 6ketoPGF(1alpha). Indomethacin (0.7 +/- 0.2 microg/ml) produced a significantly greater fall in ductus blood flow than celecoxib and tended to have a greater effect on ductus resistence in vivo. We conclude that caution should be used when recommending COX-2 inhibitors for use in pregnant women, because COX-2 appears to play a significant role in maintaining patency of the fetal ductus arteriosus.

6-Ketoprostaglandin F1 alpha↗

Sonic hedgehog-mediated ventralization disrupts formation of the midbrain-hindbrain junction in the chick embryo.

The secreted signaling molecule Sonic hedgehog (Shh) plays critical roles in pattern formation of the vertebrate central nervous system. During neurulation, Shh is produced by the ventral midline mesoderm as well as by the ventral neural tube, and its activity is required for the determination of ventral characteristics along the anterior-posterior neuraxis. The morphological boundary between midbrain and hindbrain, the isthmus, is an important tissue organizer that regulates the development of both the midbrain and the anterior hindbrain. In this study, we report that retrovirus-mediated misexpression of Shh in the early chick neural tube disrupts formation of the boundary between the midbrain and the hindbrain, and causes a fusion of the bilateral cerebellum primordia. Dorsally expressed Shh signals induce ectopic transcription of its receptor Ptc1 in the midbrain and the hindbrain. The expression of several genes (Noggin, Lmx1, BMP7) along the dorsal midline of the midbrain is abolished, and ventral or lateral markers (HNF3 beta, Ptc1, ELF1) are induced in the dorsal brain. Furthermore, the normally restricted expression of two genes (En1 and Pax2) in the mid/hindbrain junction region are expanded, reflecting the morphological defects. These results suggest that maintaining proper dorsal-ventral patterns of the neural tube is essential for normal development of the mid/hindbrain region.

Animals↗

Glottographic phase difference in recurrent nerve paralysis.

Phase measures with simultaneously recorded electroglottography (EGG) and photoglottography (PGG) signals have been studied in canine models and found to be sensitive to the effect of recurrent laryngeal nerve (RLN) paralysis on vocal fold vibration. This study examined the usefulness of this type of measure in clinical application. The combined glottographic signals were obtained from 5 men with a diagnosis of unilateral RLN paralysis and 5 age-matched controls. In the patient group, EGG waveforms were found to have a consistent phase delay in relation to PGG. A measure of the overall glottographic phase difference (GPD) was found to significantly distinguish the control group (mean GPD = 0.2371 ms) from the patient group (mean GPD = -0.2765 ms). A validity analysis performed on 19 subjects with or without unilateral RLN paralysis confirmed that the GPD test had a relatively high efficiency (91.7%) in detecting unilateral RLN paralysis in the male population.

Adult↗

The design, implementation, and acceptance of a primary care-based intervention to prevent depression relapse.

OBJECTIVE: This article describes the conceptual underpinnings, implementation, and participation rates of a twelve-month low-intensity primary care-based intervention to prevent depression relapse. The intervention was designed to address the inherent problems in delivery of effective maintenance treatment in a population based sample of primary care patients. METHODS: Patients at high risk of relapse based on psychiatric history who recovered from depression six to eight weeks after initiation of pharmacotherapy by their primary care physician were eligible; 194 were randomized to receive the intervention. The intervention combined education about depression, motivation-enhancing shared decision-making regarding the use of maintenance pharmacotherapy, and cognitive-behavioral strategies. The program included two visits with a Depression Prevention Specialist working in tandem with the primary care physician at the primary care clinic, with supervision and back up from a consulting psychiatrist, proactive follow-up telephone calls and mailed personalized feedback. RESULTS: Ninety-three percent of patients attended both in-person visits; 97 percent attended one visit. Eighty percent of patients completed all three follow-up telephone calls, and 85 percent returned at least one mailed feedback form; 48 percent returned all four forms. Offered a menu of options for self-management, most patients chose medication as well as a variety of behavioral strategies. At six months, 72 percent ofpatients and at twelve months 62 percent of patients remained on antidepressant medication. CONCLUSIONS: We conclude that it is feasible to integrate a low intensity, twelve-month relapse prevention intervention for depression into a primary care clinic.

Antidepressive Agents↗