PubMed Health⌕ Search

Biomedical subjects

E L Knight

Publications and source records attributed to E L Knight.

At least 19 recordsLinked to original sources
PubMed2001

Paradoxical relations of drug treatment with mortality in older persons.

Medication use patterns provide popular surrogate measures of disease, yet selective under-use of drugs by elderly patients with potentially unmeasured comorbidity may lead to artifactual "protective" associations between use of specific drugs and mortality. We examined the relation between use of 20 common classes of drugs and mortality among the 129,111 residents of New Jersey 65-99 years of age who had at least one hospitalization during the years 1991-1994 and filled prescriptions through either Medicaid or that state's Pharmacy Assistance for the Aged and Disabled program. Each study drug class was used by more than 5,000 subjects during the 120 days before hospitalization; 41,930 subjects died in the hospital or during the year after discharge. Users of drugs from each of seven therapeutic classes had reduced age- and sex-adjusted rates of death relative to non-users: lipid-lowering agents, nonsteroidal anti-inflammatory agents, beta blockers, thiazides, glaucoma drugs, calcium channel blockers, and anti-anxiety drugs. Adjustment for comorbidity and polypharmacy had little effect on these results. We found similar results in a separate nonhospitalized cohort of 132,071 elderly persons. Much of this observed association appears to be nonetiologic. These findings raise concerns about using observational studies in high-risk populations to infer associations between drug use and outcomes.

Age Factors↗
PubMed2001

Predictors of uncontrolled hypertension in ambulatory patients.

Hypertension remains poorly controlled in the United States. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. We studied antihypertensive medication use, comorbidity, and blood pressure measurements for 525 hypertensive patients in 3 different healthcare systems over a 1-year period. We concomitantly conducted comprehensive patient interviews covering demographic factors, knowledge of hypertension and its treatment, and medication side effects. Ordinal logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65+/-11 years. Mean systolic blood pressure (SBP) was 143+/-15 mm Hg; and mean diastolic blood pressure (DBP), 80+/-9 mm Hg. Only 39% (203/525) of patients had mean blood pressure <140/90 mm Hg during the study period; about half (257/525) had stage 1 hypertension (mean SBP 140 to 159 mm Hg and/or mean DBP 90 to 99 mm Hg), and 12% (65/525) had stage 2 or greater hypertension (SBP >160 mm Hgand/or DBP >100 mm Hg). Multivariate analysis revealed several independent predictors of poor control: older age, multi-drug regimens, lack of knowledge by the patient of their target SBP, and a report of antihypertensive drug side effects. Patients with angina had a higher likelihood of adequate blood pressure control. Fewer than 40% of the treated patients studied had a mean blood pressure </=140/90 mm Hg, and specific patient-related factors appear to predict poor control. Some of these may be amenable to modification. Further identification of patients at risk of poor control can lead to targeted interventions to improve management.

Aged↗
PubMed2001

Consumer-run service participation, recovery of social functioning, and the mediating role of psychological factors.

OBJECTIVE: This study examined the relationship between participation in consumer-run services and recovery of social functioning among persons diagnosed as having serious mental illness. It also assessed the role of psychological factors in mediating this relationship. METHODS: Research questions investigated were whether involvement in consumer-run services is positively associated with recovery when premorbid and demographic factors are controlled for, whether psychological factors are positively associated with recovery irrespective of involvement in consumer-run services, and whether the relationship between involvement in consumer-run services and recovery is mediated by the psychological factors. The factors examined were self-efficacy, hopefulness, and active coping strategies. Sixty participants with a past or present diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder and at least one past psychiatric hospitalization were recruited from a community mental health center and two consumer-run programs. Data were collected on hopefulness, self-efficacy, coping strategies, social functioning, and premorbid and demographic characteristics. RESULTS: Findings indicated that participants involved in consumer-run services had better social functioning than those involved only in traditional mental health services, that psychological variables were significantly associated with social functioning, and that the relationship between involvement in consumer-run services and social functioning was partly mediated by the use of more problem-centered coping strategies. Premorbid and demographic factors did not account for the relationship between psychosocial variables and social functioning, although education was a significant predictor of social functioning. CONCLUSIONS: The findings support the view that psychosocial factors may play a role in facilitating good community adjustment for individuals diagnosed as having serious mental illness.

Adaptation, Psychological↗
PubMed2000

Chimeric VEGFRs are activated by a small-molecule dimerizer and mediate downstream signalling cascades in endothelial cells.

Despite much interest in vascular endothelial growth factor (VEGF) and its receptors (VEGFRs -1 and -2), VEGF-induced signalling cascades remain incompletely defined. Attempts to assign individual responses to a particular receptor have used either transfected cell lines, receptor-specific growth factors or antisense oligonucleotides. Such studies have attributed the majority of VEGF-induced responses to activation of VEGFR-2. As a consequence of poor growth factor-induced VEGFR-1 autophosphorylation however, observations from these studies may instead reflect the relative activation of the two receptors. We have generated novel chimeric VEGF receptors in which the dimerization domain of the B subunit of DNA gyrase is fused to the cytoplasmic domain of VEGFRs -1 and -2. When expressed in porcine aortic endothelial cells, both chimeric VEGFR-1 and -2 autophosphorylate in response to addition of the small-molecule dimerizing agent, coumermycin. Once activated, both receptors induce downstream signalling cascades, exemplified here by the activation of MAPK, PLCgamma and PKB/Akt. Furthermore, we demonstrate that the Y1175 residue of VEGFR-2 is essential for the activation of PLCgamma mediated by this chimeric receptor. In contrast to previous reports which show a limited ability of VEGFR-1 to mediate signalling cascades, we show that once sufficiently activated, VEGFR-1 signals in a similar manner to VEGFR-2 in endothelial cells.

Aminocoumarins↗
PubMed2000

The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growth-factor receptor KDR in transfected cells.

Despite much progress in recent years, the precise signalling events triggered by the vascular-endothelial-growth-factor (VEGF) receptors, fms-like tyrosine kinase (Flt1) and kinase insert domain-containing receptor (KDR), are incompletely defined. Results obtained when Flt1 and KDR are individually expressed in fibroblasts or porcine aortic endothelial cells have not been entirely consistent with those observed in other endothelial cells expressing both receptors endogenously. It has also been difficult to demonstrate VEGF-induced phosphorylation of Flt1, which has led to speculation that KDR may be the more important receptor for the mitogenic action of VEGF on endothelial cells. In an attempt to identify physiologically important effectors which bind to KDR, we have screened a yeast two-hybrid mouse embryo library with the cytoplasmic domain of KDR. Here we describe the identification of the adaptor protein, Shc-like protein (Sck), as a binding partner for KDR. We demonstrate that this interaction requires phosphorylation of KDR, and identify the binding site for the Src-homology 2 (SH2) domain as tyrosine-1175 of KDR. We have also shown that the SH2 domain of Sck, but not that of Src-homology collagen protein (Shc), can precipitate phosphorylated KDR from VEGF-stimulated porcine aortic endothelial cells expressing KDR, and that an N-terminally truncated Sck protein can associate with KDR, in a phosphorylation-dependent fashion, when co-expressed in human embryonic kidney 293 cells. Furthermore, we demonstrate that in the two-hybrid assay, both Shc and Sck SH2 domains can associate with the related receptor Flt1.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Failure of evidence-based medicine in the treatment of hypertension in older patients.

OBJECTIVE: Throughout the 1990s, the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommended initial antihypertensive therapy with a thiazide diuretic or a beta-blocker based on evidence from randomized, controlled trials, unless an indication existed for another drug class. The committee also recommended beta-blockers in hypertensive patients with a history of myocardial infarction (MI), and angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure (CHF). Our objective was to determine whether prescribing practices for older hypertensive patients are consistent with evidence-based guidelines. METHODS: We examined prescription patterns from January 1, 1991 through December 31, 1995 for 23,748 patients 65 years or older with a new diagnosis of hypertension from the New Jersey Medicaid program and that state's Pharmacy Assistance for the Aged and Disabled program (PAAD). We linked drug use data with information on demographic variables and comorbid medical conditions. RESULTS: During the study period, calcium channel blockers were the most commonly prescribed initial therapy for hypertension (41%), followed by ACE inhibitors (24%), thiazide diuretics (17%), and beta-blockers (10%). Eliminating patients with diabetes mellitus, CHF, angina, or history of MI did not substantially affect these results. Overall, initial use of a thiazide declined from 22% in 1991 to 10% in 1995, while initial use of a calcium channel blocker increased from 28% to 43%, despite publication during these years of studies demonstrating a benefit of thiazides in older patients. Only 15% of older hypertensive patients with a history of MI received beta-blockers. CONCLUSIONS: Prescribing practices for older hypertensive patients are not consistent with evidence-based guidelines. Interventions are needed to encourage evidence-driven prescribing practices for the treatment of hypertension.

Aged↗
PubMed2000

Adherence to guidelines for oral anticoagulation after venous thrombosis and pulmonary embolism.

OBJECTIVE: Guidelines for oral anticoagulation after deep venous thrombosis (DVT) or pulmonary embolism (PE) have recommended that patients be anticoagulated for at least 3 months after hospital discharge. We sought to determine whether this recommendation was being followed and what patient characteristics predict a shorter than recommended duration of therapy. DESIGN: Retrospective cohort study using linked health care claims data. SETTING: Routine clinical practice. PATIENTS: Five hundred seventy-three members of New Jersey's Medicaid or Pharmacy Assistance for the Aged and Disabled programs aged 65 years and older who were hospitalized for DVT or PE between January 1, 1991 and June 30, 1994. RESULTS: Of the 573 patients, 129 (23%) filled prescriptions covering less than 90 days of oral anticoagulant therapy. In multivariate models, African-American race was associated with an increased risk of a shorter than recommended duration of therapy (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14 to 3.08), but age and gender were not. Patients who used anticoagulants in the year prior to admission were less likely to have a short duration of therapy (OR, 0.30; 95% CI, 0.12 to 0.78), than were patients with PE (OR, 0.58; 95% CI, 0.38 to 0.88). CONCLUSIONS: Nearly a quarter of those anticoagulated following DVT or PE received therapy for less than the recommended length of time after hospital discharge, with African Americans more likely to have a shorter than recommended course of treatment. Further research is needed to evaluate the causes of shorter than recommended duration of therapy and racial disparities in anticoagulant use.

Black or African American↗
PubMed1999

Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD)

BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE: To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.

Adrenergic beta-Antagonists↗
PubMed1999

Atrial natriuretic peptide and the development of congestive heart failure in the oldest old: a seven-year prospective study.

BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic heart failure and correlate with invasively measured left heart pressures. OBJECTIVE: To examine the association between plasma ANP level and the subsequent development of congestive heart failure (CHF) in older subjects with no history of CHF. DESIGN: A 7-year, prospective, blinded, cohort study. SETTING: A life care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred fifty-six frail older subjects (mean age 88 +/- 7) with no history of CHF at study entry. MAIN OUTCOME MEASURE: Clinical episodes of CHF with confirmatory chest roentgenogram findings. Cox proportional hazard analyses were performed to examine the relationship between ANP levels and the development of CHF while controlling for 19 clinical, physical, and laboratory parameters. A Kaplan-Meier estimator (log-rank test) was used to determine if the development of CHF differed by tertile of ANP. RESULTS: During the follow-up period, 32% of the cohort developed CHF. The mean ANP level in the CHF group was 95 pmol/L +/- 11 pmol/L versus 60 pmol/L +/- 5 pmol/L in the no CHF group (two tailed t test P = .005). On multivariate analysis, a high ANP level was found to be associated significantly (P = .01) with the development of CHF. CONCLUSIONS: There is a statistically significant association between ANP level and the subsequent development of CHF in frail older individuals with no history of CHF.

Aged↗
PubMed1999

Effects of age and gender on autonomic control of blood pressure dynamics.

Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age- and gender- related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60 degrees head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (-10.2+/-2 versus -1.2+/-3 mm Hg; P=0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P=0.02). Upright plasma norepinephrine was lower in women (P=0.02). Women had greater supine high-frequency R-R interval power than men (P=0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P=0.01), despite higher supine (P=0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

Adult↗
PubMed1998

Atrial natriuretic peptide level contributes to a model of future mortality in the oldest old.

OBJECTIVES: To determine if atrial natriuretic peptide (ANP) level is associated with mortality in the oldest old and to develop a comprehensive model of mortality in the oldest old using clinical and laboratory parameters. DESIGN: Prospective cohort study with 7 years of follow-up. SETTING: A 725-bed life care facility. PARTICIPANTS: 282 frail older individuals (mean age 88, range 70-102). MEASUREMENTS: Variables measured included age, gender, Charlson Comorbidity Index, functional measurements, weight, blood pressure, and multiple laboratory variables, including ANP. Main outcome measurement was death. RESULTS: Eighty-four percent (237/282) of subjects died during the 7-year follow-up period. On univariate analysis, the risk ratio (RR) for ANP tertile was 1.28. On bivariate analysis, adjusting for the development of congestive heart failure, the RR was 1.22. On multivariate analysis, the following variables were associated with mortality: ANP tertile (RR 1.24), age (RR 1.04), female gender (RR 0.43), Charlson Comorbidity Index score (RR 1.13), mentation score (RR 1.27), BUN/Cr ratio (RR 1.04), albumin level (RR 0.63), and hemoglobin level (RR 0.84). CONCLUSIONS: ANP level and other variables are independent risk factors for mortality in frail individuals. ANP level may indicate homeostatic failure to adapt to fluid volume changes or may reflect subclinical heart disease. ANP level contributes to a multivariate model of mortality in frail older individuals.

Aged↗
PubMed1986

Renal cell carcinoma in pregnancy.

Renal cell carcinoma is the most common renal neoplasm associated with pregnancy. The most common presenting symptoms are pain and a palpable mass. Although renal neoplasms in pregnancy are rare, the pregnancy demands special consideration in the methods of diagnostic evaluation. The relationship between renal cell carcinoma and pregnancy is unclear. Treatment is usually radical nephrectomy regardless of the stage of pregnancy. Two new cases are presented with a review of the literature.

Adult↗
PubMed1979

Leukemic infiltration of penis.

Leukemic infiltration of the urinary tract is most common in the kidneys. Other areas are involved much less frequently. We report a case of leukemic infiltration of the penis.

Aged↗