Biomedical subjects

Lloyd J Edwards

Publications and source records attributed to Lloyd J Edwards.

12 recordsLinked to original sources

PubMed2006

A method for fitting regression splines with varying polynomial order in the linear mixed model.

The linear mixed model has become a widely used tool for longitudinal analysis of continuous variables. The use of regression splines in these models offers the analyst additional flexibility in the formulation of descriptive analyses, exploratory analyses and hypothesis-driven confirmatory analyses. We propose a method for fitting piecewise polynomial regression splines with varying polynomial order in the fixed effects and/or random effects of the linear mixed model. The polynomial segments are explicitly constrained by side conditions for continuity and some smoothness at the points where they join. By using a reparameterization of this explicitly constrained linear mixed model, an implicitly constrained linear mixed model is constructed that simplifies implementation of fixed-knot regression splines. The proposed approach is relatively simple, handles splines in one variable or multiple variables, and can be easily programmed using existing commercial software such as SAS or S-plus. The method is illustrated using two examples: an analysis of longitudinal viral load data from a study of subjects with acute HIV-1 infection and an analysis of 24-hour ambulatory blood pressure profiles.

Blood Pressure Monitoring, Ambulatory↗

PubMed2006

Comparing United States versus international medical school graduate physicians who serve African- American and White elderly.

OBJECTIVE: To examine the relationship that international medical school graduates (IMGs) in comparison with United States medical school graduates (USMGs) have on health care-seeking behavior and satisfaction with medical care among African-American and white elderly. DATA SOURCES: Secondary data analysis of the 1986-1998 Piedmont Health Survey of the Elderly, Established Populations for the Epidemiological Study of the Elderly, a racially oversampled urban and rural cohort of elders in five North Carolina counties. STUDY DESIGN: Primary focus of analyses examined the impact of the combination of elder race and physician graduate status across time using a linear model for repeated measures analyses and chi2 tests. Separate analyses using generalized estimating equations were conducted for each measure of elder characteristic and health behavior. The analytic cohort included 341 physicians and 3,250 elders (65 years old and older) in 1986; by 1998, 211 physicians and 1,222 elders. DATA COLLECTION/EXTRACTION METHODS: Trained personnel collected baseline measures on 4,162 elders (about 80 percent responses) through 90-minute in-home interviews. PRINCIPAL FINDINGS: Over time, IMGs treated more African-American elders, and those who had less education, lower incomes, less insurance, were in poorer health, and who lived in rural areas. White elders with IMGs delayed care more than those with USMGs. Both races indicated being unsure about where to go for medical care. White elders with IMGs were less satisfied than those with USMGs. Both races had perceptions of IMGs that relate to issues of communication, cultural competency, ageism, and unnecessary expenses. CONCLUSION: IMGs do provide necessary and needed access to medical care for underserved African Americans and rural populations. However, it is unclear whether concerns regarding cultural competency, communication and the quality of care undermine the contribution IMGs make to these populations.

Black or African American↗

PubMed2005

Physician-patient racial concordance, continuity of care, and patterns of care for hypertension.

To assess the effects of physician-patient racial concordance and continuity of care on hypertension outcomes, we described patterns of care for hypertension; we used cross-tabulations and repeated measures (generalized estimating equations) analyses with panel survey data from elderly persons interviewed and examined in 1987 and 1990. Continuity of care was associated with recognition of hypertension, receipt of medication, and lower incidence of undetected hypertension. Physician race had little effect, but continuity is important for successful management of hypertension in older persons.

Aged↗

PubMed2005

Naïve T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function.

A key determinant of T cell dynamics in HIV-1 infection is the status of thymic function. To date, most studies of the impact of HIV-1 on the thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infection. In this study, we have probed the status of thymic function and peripheral naive T cells in patients with acute HIV-1 infection diagnosed 18-72 days after the onset of symptoms. We found that peripheral CD4 and CD8 T cell proliferation was initially elevated, then waned over time. The fall in T cell proliferation correlated with a reduction in HIV-1 viral RNA levels and a rise in peripheral blood CD4+ CD25+ T cells. In spite of elevated T cell proliferation early on in primary HIV-1 infection, levels of naive phenotype CD4 and CD8 T cells and T cell receptor excision circle positive cells (sjTREC(+)) remained constant. Taken together with the observation that T cell proliferation normally dilutes peripheral T cell episomal sjTREC levels, these data suggested that thymopoiesis contributes to maintenance of the naive T cell pool during the earliest stages of HIV-1 infection (18-72 days).

Adult↗

PubMed2005

Effect of olanzapine on body composition and energy expenditure in adults with first-episode psychosis.

OBJECTIVE: Weight gain is a commonly observed adverse effect of atypical antipsychotic medications, but associated changes in energy balance and body composition are not well defined. The authors report here the effect of olanzapine on body weight, body composition, resting energy expenditure, and substrate oxidation as well as leptin, insulin, glucose, and lipid levels in a group of outpatient volunteers with first-episode psychosis. METHOD: Nine adults (six men and three women) experiencing their first psychotic episode who had no previous history of antipsychotic drug therapy began a regimen of olanzapine and were studied within 7 weeks and approximately 12 weeks after olanzapine initiation. RESULTS: After approximately 12 weeks of olanzapine therapy, the median increase in body weight was 4.7 kg, a significant increase of 7.3% from first observation. Body fat, measured by dual-energy x-ray absorptiometry, increased significantly, with a propensity for central fat deposition. Lean body mass and bone mineral content did not change. Resting energy expenditure, measured by indirect calorimetry, did not change. Respiratory quotient significantly increased 0.12 with olanzapine and was greatest in those who gained >5% of their initial weight. Fasting insulin, C-peptide, and triglyceride levels significantly increased, but there were no changes in glucose levels; total, high density lipoprotein, or low density lipoprotein cholesterol levels; or leptin levels. CONCLUSIONS: Olanzapine appears to have induced an increase in central body fat deposition, insulin, and triglyceride levels, suggesting the possible development of insulin resistance. The decrease in fat oxidation may be secondary or predispose patients to olanzapine-induced weight gain.

Adipose Tissue↗

PubMed2004

Obesity and type 2 diabetes mellitus: a population-based study of adolescents.

A cross-sectional, population-based study was conducted on 1,647 Turkish adolescents to determine the prevalence of obesity, impaired fasting glucose (IFG) and type 2 diabetes mellitus (DM2), and to determine whether the recent increase in DM2 prevalence in some countries is applicable to this population. Information was gathered through a questionnaire. All children were screened with physical examination and fasting plasma glucose. 10.7% of adolescents were overweight (BMI 85-95th percentile) and 3.6% were obese (BMI > or =95th percentile). Mean BMI was 20.25 +/- 3.31 kg/m2 with maximum BMI 35.88 kg/m2. No child was diagnosed with DM2; 1.96% had IFG (110-126 mg/dl). No significant relationship was found between IFG and obesity, socio-economic status (SES) or family history of DM. The risk of obesity was increased among children with family history of DM or obesity, and among those who had low physical activity and were of high SES level. This analysis represents the population-based data upon which future studies will be based.

Adolescent↗

PubMed2003

Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline.

Choline is an essential nutrient for humans and is derived from the diet as well as from de novo synthesis involving methylation of phosphatidylethanolamine catalysed by the enzyme phosphatidylethanolamine N -methyltransferase (PEMT). This is the only known pathway that produces new choline molecules. We used mice with a disrupted Pemt-2 gene (which encodes PEMT; Pemt (-/-)) that have previously been shown to possess no hepatic PEMT enzyme. Male, female and pregnant Pemt (-/-) and wild-type mice ( n =5-6 per diet group) were fed diets of different choline content (deficient, control, and supplemented). Livers were collected and analysed for choline metabolites, steatosis, and apoptotic [terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)] positive cells. We found that, in livers of Pemt (-/-) mice fed any of the diets, there was hepatic steatosis and significantly higher occurrence of TUNEL positive cells compared with wild-type controls. In male, female and pregnant mice, liver phosphatidylcholine concentrations were significantly decreased in Pemt (-/-) choline deficient and in Pemt (-/-) choline control groups but returned to normal in Pemt (-/-) choline supplemented groups. Phosphocholine concentrations in liver were significantly diminished in knockout mice even when choline was supplemented to above dietary requirements. These results show that PEMT normally supplies a significant portion of the daily choline requirement in the mouse and, when this pathway is knocked out, mice are unable to attain normal concentrations of all choline metabolites even with a supplemental source of dietary choline.

Animals↗

PubMed2002

Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis.

Nontuberculous mycobacteria (NTM) are potential respiratory pathogens in cystic fibrosis (CF). To assess the species-specific prevalence and risk factors for acquisition, we conducted a prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Almost 10% of patients with CF who were 10 years or older were included (n = 986). The overall prevalence of NTM in sputum was 13.0% (range by center, 7-24%). Mycobacterium avium complex (72%) and Mycobacterium abscessus (16%) were the most common species. When compared with patients with CF without NTM, culture-positive subjects were older (26 vs. 22 years, p < 0.001), had a higher FEV1 (60 vs. 54%, p < 0.01), higher frequency of Staphylococcus aureus (43 vs. 31%, p < 0.01), and lower frequency of Pseudomonas aeruginosa (71 vs. 82%, p < 0.01). Molecular typing revealed that almost all patients within each center had unique NTM strains. In summary, NTM are common in patients with CF, but neither person-to-person nor nosocomial acquisition explained the high prevalence. Older age was the most significant predictor for isolation of NTM. The clinical significance of NTM in CF is incompletely defined, but patients with these organisms should be monitored with repeat cultures.

Adolescent↗

PubMed2002

Screening for diabetes in an outpatient clinic population.

BACKGROUND: Opportunistic disease screening is the routine, asymptomatic disease screening of patients at the time of a physician encounter for other reasons. While the prevalence of unrecognized diabetes in community populations is well known, the prevalence in clinical populations is unknown. OBJECTIVE: To describe the prevalence, predictors, and clinical severity of unrecognized diabetes among outpatients at a major medical center. DESIGN AND SETTING: A cross-sectional observational study at the Durham Veterans Affairs Medical Center. SUBJECTS: Outpatients without recognized diabetes (N=1,253). METHODS: We screened patients for diabetes by using an initial random Hemoglobin A1c (HbA1c) measurement, and then obtaining follow-up fasting plasma glucose (FPG) for all subjects with HbA1c > or =6.0%. A case of unrecognized diabetes was defined as either HbA1c > or =7.0% or FPG > or =7 mmol/L (126 mg/dL). Height and weight were obtained for all subjects. We also obtained resting blood pressure, fasting lipids, and urine protein in subjects with HbA1c > or =6.0%. RESULTS: The prevalence of unrecognized diabetes was 4.5% (95% confidence interval [CI], 3.4 to 5.7). Factors associated with unrecognized diabetes were the diagnosis of hypertension (adjusted odds ratio [OR], 2.5; P=.004), weight >120% of ideal (adjusted OR, 2.2; P=.02), and history of a parent or sibling with diabetes (adjusted OR, 1.7; P=.06). Having a primary care provider did not raise or lower the risk for unrecognized diabetes (P=.73). Based on the new diagnosis, most patients (61%) found to have diabetes required a change in treatment either of their blood sugar or comorbid hypertension or hyperlipidemia in order to achieve targets recommended in published treatment guidelines. Patients reporting a primary care provider were no less likely to require a change in treatment (P=.20). CONCLUSIONS: If diabetes screening is an effective intervention, opportunistic screening for diabetes may be the preferred method for screening, because there is substantial potential for case-finding in a medical center outpatient setting. A majority of patients with diabetes diagnosed at opportunistic screening will require a change in treatment of blood sugar, blood pressure, or lipids to receive optimal care.

Aged↗

PubMed2002

HIV infection: treatment outcomes in older and younger adults.

OBJECTIVES: To determine the effect of antiretroviral therapy (ART) on the immunological and virological outcomes of older human immunodeficiency virus (HIV)-infected patients compared with younger HIV-infected patients. DESIGN: Matched (1:2) retrospective case-control study (1993-1999). SETTING: Duke University Infectious Diseases Clinic. PARTICIPANTS: One hundred one older patients, mean age 56.7 (range 50-79) and 202 younger patients, mean age 32.8 (range 21-39). Patients were matched on baseline CD4+ cell count and date of clinic entry. MEASUREMENTS: The virological and immunological outcomes were viral suppression (HIV ribonucleic acid (RNA) level < or =400 copies/ml) and change in CD4+ cell count. To estimate differences in antiretroviral drug exposure, the percentage of patients on ART overall and by drug class was compared. To assess antiretroviral drug exposure further, the percentage of patients having interruptions in ART was compared. RESULTS: The older and younger groups had similar baseline CD4+ cell counts (332 vs 306 cells/mm3; P =.31) and similar increases in CD4+ cell counts (+3.47 vs +4.60 cells/mm3/month; P =.37) over a mean +/- standard deviation of 2.4 +/- 1.7 years of follow-up. The older group had a higher percentage of patients with current plasma HIV RNA levels less than 400 (46% vs 34%; P =.05). The groups had similar rates of non-nucleoside reverse transcriptase, nucleoside reverse transcriptase, and protease inhibitor use. The older group had fewer interruptions in ART than the younger group (11% vs 26%; P =.01). CONCLUSIONS: Older HIV-infected patients responded well to ART, with a significantly greater percentage achieving a current plasma HIV RNA below detectable limits. Older patients experienced similar increases in CD4+ cell count as younger matched controls. Older patients were less likely to interrupt ART, which suggests better adherence and/or tolerance and may explain the higher rate of HIV RNA suppression.

Adult↗

PubMed2002

Deficiency in methionine, tryptophan, isoleucine, or choline induces apoptosis in cultured cells.

Cells in culture die by apoptosis when deprived of the essential nutrient choline. We now report that cells (both proliferating PC12 cells and postmitotic neurons isolated from fetal rat brains) undergo apoptosis when deprived of other individual essential nutrients (methionine, tryptophan or isoleucine). In PC12 cells, deficiencies of each nutrient independently led to ceramide accumulation and to caspase activation, both recognized signals of several apoptotic pathways. A similar profile of caspases was activated in PC12 cells deprived of choline, methionine, tryptophan or isoleucine. More than one caspase was involved and these caspases appeared to transmit parallel signals for apoptosis induction because only broad-spectrum caspase inhibitors, but not inhibitors for specific individual caspases inhibited apoptosis in choline- or methionine-deprived cells. The induction of these caspase-dependent apoptosis pathways likely did not involve the same upstream signals. Choline deficiency perturbed choline metabolism but did not affect protein synthesis, whereas amino acid deficiencies inhibited protein synthesis but did not perturb choline metabolism. In addition, a subclone of PC12 cells that was resistant to choline deficiency-induced apoptosis was not resistant to tryptophan deficiency-induced apoptosis. These observations suggest that deficiency of each studied nutrient activates different pathways for signaling apoptosis that ultimately converge on a common execution pathway.

Amino Acids↗

PubMed2001

Impact of sodium and ultrafiltration profiling on hemodialysis-related symptoms.

Dialysate sodium and ultrafiltration profiling are two methods to reduce symptoms during hemodialysis. The objective of the study was to determine the efficacy of combining these techniques to reduce symptoms in chronic hemodialysis patients. Blood volume changes were measured to determine whether any benefit of profiling could be explained through this mechanism. Patients were randomized to profiled dialysate sodium and ultrafiltration or constant dialysate sodium and ultrafiltration. The study was a two-period, two-treatment, crossover design with repeated measures. The primary outcome was hypotension and/or symptomatic events observed by the dialysis nurse. Secondary outcomes were symptom survey scores, weights, BP, and blood volume changes. Thirty-three patients were randomized. On standard treatment, 30.6% of dialysis sessions were symptomatic compared with 20.4% on profiled treatments. The odds ratio for the development of hypotension or symptomatic event on profiled treatments was 0.61 (95% confidence interval, 0.39 to 0.96) compared with standard treatment. Patients had lower symptom scores by questionnaire in both the intradialytic and the interdialytic periods during profiled treatments. Predialysis weight was greater during profiled treatments by 0.3 kg (P: = 0.008), but there were no differences in postdialysis weight, BP, or thirst. There was no difference in maximum decrease in blood volume during the two treatments (standard, -11.2%; profiled, -10.0%; P: = 0.08), but there was a significant difference in the rate of change in blood volume (standard, -2.96%/h; profiled, -1.96%/h; P: < 0.001). Decrease in blood volume, rate of change in blood volume, and predialysis weights were not associated with hypotension or symptomatic dialysis sessions. In conclusion, dialysate sodium and ultrafiltration profiling significantly reduces hemodialysis-related symptoms. Profiling reduces the slope of the blood volume curve during dialysis, but blood volume changes are not predictive of symptomatic events for an individual patient.

Aged↗