Biomedical subjects

Darren B Taichman

Publications and source records attributed to Darren B Taichman.

8 recordsLinked to original sources

PubMed2006

Formation and validation of a telephone battery to assess cognitive function in acute respiratory distress syndrome survivors.

PURPOSE: Describe initial development and validation of a test battery composed of established instruments designed to detect, via telephone interview, cognitive abnormalities in survivors of acute respiratory distress syndrome. METHODS: Two cross-sectional studies were performed, including the following phases: (1) initial battery construction, (2) feasibility, (3) item reduction, (4) convergent and divergent validity, and (5) telephone administration compared with in-face interviews in a separate population. RESULTS: There was a broad range of cognitive function detected in the derivation population, and all subjects completed the interview. There was convergence of cognitive impairment with moderate/severe anxiety (P = .008), the Sickness Impact Profile Psychosocial Summary Score (mean difference, 15.3; 95% CI, 7.74-22.9; P = .0001), and the mental health domains of the Short Form 36. Subjects with cognitive impairment had no detectable difference in the physical function domains of the Short Form 36. When administered to the validation population, telephone tests of memory, attention, reasoning, and executive functions had good intraclass correlation with the in-face interviews (P < .01). CONCLUSIONS: Detection of cognitive abnormalities in acute respiratory distress syndrome survivors using a telephone-administered test battery derived from standard cognitive tests is feasible and has evidence of construct validity. This battery may be useful as a research tool when in-face interviews are not feasible.

Adult↗

PubMed2005

Health-related quality of life in patients with pulmonary arterial hypertension.

BACKGROUND: Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about health-related quality of life and its determinants in patients with pulmonary arterial hypertension. METHODS: Health-related quality of life was evaluated in a cross sectional study of 155 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with health-related quality of life scores. RESULTS: Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic ("primary") pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with better health-related quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with health-related quality of life scores. No differences in health-related quality of life were found between patients who were being treated with calcium channel antagonists, bosentan or continuously infused epoprostenol at the time of quality of life assessment. CONCLUSION: Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. Specific associations with impaired health-related quality of life suggest potential areas for targeted intervention.

Adolescent↗

PubMed2005

Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension.

BACKGROUND: The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. METHODS: 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. RESULTS: For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p < or = 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. CONCLUSION: Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.

Adult↗

PubMed2005

Hemodynamics and survival of patients with portopulmonary hypertension.

It is not known whether patients with pulmonary arterial hypertension associated with portal hypertension (portopulmonary hypertension (PPHTN) have different disease characteristics from those of patients with other forms of pulmonary arterial hypertension. We performed a retrospective cohort study of patients with PPHTN and patients with pulmonary arterial hypertension that was idiopathic, familial, or associated with anorexigen use (IPAH) to determine whether hemodynamics or survival were different between these groups. We included consecutive patients who underwent initial pulmonary artery catheterization and vasodilator testing at our center between January 1997 and May 2001 and who were followed until January 2004. Patients with PPHTN (N = 13) had a higher cardiac index and lower pulmonary vascular resistance than patients with IPAH (N = 33) (P < or = 0.001). Right atrial pressure and pulmonary artery pressure were similar between the groups. Patients with PPHTN had a higher risk of death in multivariate analysis (hazard ratio: [HR] = 2.8, 95% CI 1.04-7.4; P = 0.04). These findings were not affected by adjustment for differences in laboratory values, hemodynamics, or therapy. In conclusion, patients with PPHTN have a higher risk of death than that of patients with IPAH, despite having a higher cardiac index and lower pulmonary vascular resistance. Future studies of the specific mechanisms of and therapy for pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease.

Adult↗

PubMed2003

A unique pattern of Tie1 expression in the developing murine lung.

The molecular mechanisms responsible for organ-specific differences in vascular development are not well established. Animals lacking the receptor tyrosine kinase Tie1 die of hemorrhage and pulmonary edema. Furthermore, cells lacking Tie1 are excluded from blood vessels of the mature lung. These findings suggest the importance of Tie1 in the pulmonary vasculature. We quantified the organ-specific expression of Tie1 during embryonic and postnatal murine development using both quantitative real-time polymerase chain reaction (PCR) and chemiluminescence employing a tie1.lacZ reporter. In the lung, Tie1 expression increases markedly immediately prior to birth and rises further in the newborn animal, a pattern not found in other organs. Furthermore, expression of Tie1 in the lung is also unique by its persistent increase in the adult animal. This unique pattern of Tie1 gene expression in the embryonic and mature lung supports a distinct role for Tie1 in the development and function of the pulmonary vasculature.

Animals↗

PubMed2003

Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis.

STUDY OBJECTIVES: The goal of this study was to determine whether the survival of patients with pulmonary hypertension related to systemic sclerosis (SScPH) was different from that of patients with other forms of pulmonary arterial hypertension. DESIGN: Retrospective cohort study. SETTING: Tertiary care medical center. PATIENTS: Our cohort was composed of 33 patients with pulmonary hypertension that is sporadic, familial, or related to anorexigen use (PPH) and 22 patients with SScPH who underwent initial pulmonary artery catheterization and vasodilator study at our center between January 1997 and June 2001. MEASUREMENTS AND RESULTS: Patients with SScPH had somewhat lower percentage of predicted lung volumes than patients with PPH (total lung capacity, 80% vs 92%; p = 0.06) and had lower percentage of predicted diffusion capacity of the lung for carbon monoxide (42% vs 68%; p = 0.0002). Right atrial pressure, pulmonary artery pressure, and cardiac index were similar between the groups. Patients with SScPH and PPH were treated with usual medical therapies, such as digoxin, warfarin, and continuous IV epoprostenol. Despite these similarities, the risk of death in patients with SScPH was higher than in patients with PPH (unadjusted hazard ratio, 2.9; 95% confidence interval, 1.1 to 7.8; p = 0.03). This increased risk appeared to persist after adjustment for a variety of demographic, hemodynamic, or treatment variables. CONCLUSIONS: Despite having similar hemodynamics, patients with SScPH have a higher risk of death than patients with PPH. Future studies of the mechanism and therapy of pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease.

Adult↗

PubMed2002

Characterization of Notch receptor expression in the developing mammalian heart and liver.

Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile duct paucity along with cardiovascular, skeletal, and ophthalmologic defects. The identification of JAG1 as the AGS disease gene revealed the crucial role of the Notch signaling pathway in the development of multiple organ systems in humans. Patients with identical mutations in JAG1 demonstrate extreme clinical variability, suggesting that other factors may influence the severity of the developmental defects in this disorder. We have defined the temporal and spatial expression patterns of the Notch receptor genes in the developing mammalian heart and liver in order to identify potential ligand/receptor interactions during embryogenesis. In the developing heart, both Notch1 and Notch2 are expressed in the outflow tracts and the epicardium, in specific cell populations previously shown to express JAG1. These cells are destined to undergo epithelial-to-mesenchymal transformation. In the newborn mouse liver, Notch2 and Notch3 are expressed in opposing cell populations, suggesting they play different roles in cell fate determination during bile duct development. JAG1 is also expressed in cells adjacent to those expressing Notch2, suggesting a possible ligand receptor relationship. The Notch receptors have distinct roles in cell fate determination in different organ systems.

Animals↗

PubMed2002

Notch1 and Jagged1 expression by the developing pulmonary vasculature.

The molecular mechanisms of pulmonary vascular development are poorly understood. Cell-specific developmental pathways are influenced by cell-cell signaling. Notch signaling molecules are highly conserved receptors active in many cell-fate determination systems. Recent observations of Notch molecules and a Notch ligand, Jagged1, suggest their importance in vascular morphogenesis, and particularly pulmonary vascular development. We performed a systematic evaluation of Notch1/Jagged1 gene and protein expression in the developing mouse lung from embryonic day 11 until adulthood by using quantitative PCR, immunofluorescence, and electron microscopic analysis. mRNA transcripts for Notch1-4 and Jagged1 increased progressively from early to later lung development, accompanied by a simultaneous rise in endothelial cell-specific gene expression, a pattern not seen in other organs. Notch1 mRNA was identified on both epithelial and mesenchymal structures of the embryonic lung. Immunofluorescence staining revealed the progressive acquisition of Notch1 and Jagged1 proteins by the emerging endothelium. Notch1 and Jagged1 were seen initially on well-formed, larger vessels within the embryonic lung bud and progressively on finer vascular networks. Each was also expressed on surrounding nonvascular structures. The localization of Notch1 and Jagged1 on endothelial cell surface membranes within the alveolar microvasculature was confirmed by immuno-electron microscopy. These temporal and spatial patterns in Notch1/Jagged1 gene and protein expression suggest multiple potential paths of cell-cell signaling during lung development and vascular morphogenesis.

Animals↗