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Biomedical subjects

Paul R Conlin

Publications and source records attributed to Paul R Conlin.

At least 19 recordsLinked to original sources
PubMed2006

Dietary sodium intake modulates myocardial relaxation responsiveness to angiotensin II.

Dietary sodium alters renovascular responsiveness to angiotensin II (Ang II) in normal subjects. Evidence supports a connection among dietary sodium, the rennin-angiotensin system, and myocardial function. The authors hypothesized that a similar relationship would exist in the heart, and that the pattern of responses would be qualitatively similar to the renal vasculature. Thirteen healthy volunteers (aged 38.6 +/- 4 years) entered a 2 week crossover design study (week 1, high sodium diet [HS] > 200 mmol Na/day; week 2, low sodium diet [LS], < 10 mmol Na/day) to investigate the influence of dietary sodium and Ang II on myocardial relaxation and renal blood flow (RBF). At the end of each study week, the authors assessed diastolic function (myocardial relaxation velocities [E'] using tissue Doppler imaging) and RBF (para-aminohippurate clearance) at baseline and after infusion of Ang II (3 ng/kg/min x 45 min). On HS diet, E' and RBF were higher than on LS diet (E' 14.0 +/- 1.2 vs 12.6 +/- 1.0 cm/s, P = 0.02; RBF 596 +/- 24 vs 563 +/- 26 mL/min, P = 0.02). Dietary sodium significantly modulated E' and RBF responsiveness to Ang II infusion in like manner. HS was associated with increased responsiveness compared with a blunted LS response (HS DeltaE' -1.4 +/- 0.4 cm/s vs LS DeltaE' -0.1 +/- 0.3 cm/s, P = 0.02; HS DeltaRBF -135.2 +/- 13.2 vs LS DeltaRBF -62.5 +/- 10.1 mL/min, P < 0.01). The authors describe for the first time that dietary sodium modulates myocardial relaxation and responsiveness to Ang II. It is important to consider dietary sodium intake when assessing diastolic function. Ang II may play a role in the interaction between dietary sodium and myocardial relaxation. Future research will investigate whether abnormalities in these mechanisms play a role in disorders of diastolic function.

Adult↗
PubMed2005

Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.

CONTEXT: Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. OBJECTIVE: To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. DESIGN, SETTING, AND PARTICIPANTS: Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. INTERVENTIONS: A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. MAIN OUTCOME MEASURES: Systolic blood pressure and low-density lipoprotein cholesterol. RESULTS: Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P = .01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. CONCLUSION: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00051350.

Adult↗
PubMed2005

Changes in aortic stiffness and augmentation index after acute converting enzyme or vasopeptidase inhibition.

Augmentation index (AI), a measure of enhanced wave reflection, has been proposed as a bedside measure of aortic stiffness. However, because AI is potentially sensitive to various factors other than vessel wall stiffness, the utility of AI as a stiffness indicator may be limited. To assess relations between AI and vascular properties, we used arterial tonometry and aortic Doppler flow to evaluate trough (24 hours) and peak (4 hours) pulsatile hemodynamics and pulse wave velocity in 159 individuals with systolic hypertension at the completion of a 12-week period of monotherapy with the vasopeptidase inhibitor omapatrilat (80 mg; n=75) or the converting enzyme inhibitor enalapril (40 mg; n=84). Characteristic impedance (Zc) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Systolic ejection period (SEP), timing of wave reflection, and AI were assessed from the carotid waveform. Comparable acute reductions in mean pressure were associated with greater reductions in peripheral resistance with enalapril, whereas neither drug had an acute effect on Zc. Both drugs reduced AI, but neither drug altered the timing of wave reflection. Both drugs increased heart rate and shortened SEP. Multiple regression analysis demonstrated that the acute reduction in AI was most affected by reductions in SEP and peripheral resistance. Change in AI was inversely related to change in Zc and pulse wave velocity did not enter the model. Our findings indicate that AI is a complex surrogate marker that is inversely related to changes in proximal aortic stiffness in systolic hypertension.

Adult↗
PubMed2005

Na+/Ca2+ exchanger activity modulates connective tissue growth factor mRNA expression in transforming growth factor beta1- and Des-Arg10-kallidin-stimulated myofibroblasts.

Transforming growth factor (TGF)-beta and des-Arg(10)-kallidin stimulate the expression of connective tissue growth factor (CTGF), a matrix signaling molecule that is frequently overexpressed in fibrotic disorders. Because the early signal transduction events regulating CTGF expression are unclear, we investigated the role of Ca(2+) homeostasis in CTGF mRNA expression in TGF-beta1- and des-Arg(10)-kallidin-stimulated human lung myofibroblasts. Activation of the kinin B1 receptor with des-Arg(10)-kallidin stimulated a rise in cytosolic Ca(2+) that was extracellular Na(+)-dependent and extracellular Ca(2+)-dependent. The des-Arg(10)-kallidin-stimulated increase of cytosolic Ca(2+) was blocked by KB-R7943, a specific inhibitor of Ca(2+) entry mode operation of the plasma membrane Na(+)/Ca(2+) exchanger. TGF-beta1 similarly stimulated a KB-R7943-sensitive increase of cytosolic Ca(2+) with kinetics distinct from the des-Arg(10)-kallidin-stimulated Ca(2+) response. We also found that KB-R7943 or 2',4'-dichlorobenzamil, an amiloride analog that inhibits the Na(+)/Ca(2+) exchanger activity, blocked the TGF-beta1- and des-Arg(10)-kallidin-stimulated increases of CTGF mRNA. Pretreatment with KB-R7943 also reduced the basal and TGF-beta1-stimulated levels of alpha1(I) collagen and alpha smooth muscle actin mRNAs. These data suggest that, in addition to regulating ion homeostasis, Na(+)/Ca(2+) exchanger acts as a signal transducer regulating CTGF, alpha1(I) collagen, and alpha smooth muscle actin expression. Consistent with a more widespread role for Na(+)/Ca(2+) exchanger in fibrogenesis, we also observed that KB-R7943 likewise blocked TGF-beta1-stimulated levels of CTGF mRNA in human microvascular endothelial and human osteoblast-like cells. We conclude that Ca(2+) entry mode operation of the Na(+)/Ca(2+) exchanger is required for des-Arg(10)-kallidin- and TGF-beta1-stimulated fibrogenesis and participates in the maintenance of the myofibroblast phenotype.

Blotting, Northern↗
PubMed2005

A telemedicine program for diabetic retinopathy in a Veterans Affairs Medical Center--the Joslin Vision Network Eye Health Care Model.

PURPOSE: To extend access to diabetic eye care and characterize the extent of diabetic retinopathy {DR) and other ocular findings using the Joslin Vision Network (JVN). DESIGN: Retrospective observational cohort study. METHODS: Outpatients at the Togus VA Medical Center with diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance underwent JVN protocol imaging. Images were transmitted to the Joslin Diabetes Center for grading and recommended treatment plan. RESULTS: The study included 1,219 patients (2,437 eyes); 1,536 eyes (63.0%) had no (DR), 389 (16.0%) had mild nonproliferative DR (NPDR), 105 (4.3%) moderate NPDR, 35 (1.4%) severe NPDR, 20 (0.8%) very severe NPDR, and 21 (0.9%) had proliferative DR (PDR). Regarding diabetic macular edema (DME), 1,907 eyes (78.3%) had no DME, 34 (1.4%) had early DME, and 16 (0.7%) had clinically significant macular edema (CSME). Of all patients, 354 (29.0%) had either no DR or mild NPDR in both eyes, no evidence of DME, and no significant nondiabetic findings; 679 (55.7%) had no DR in either eye, and 229 (18.8%) had mild NPDR in the more severe eye. Of the 908 patients (74.5%) with either no DR or mild NPDR in the more severe eye, 533 (58.7%) had at least one nondiabetic ocular finding necessitating referral. Finally, 320 eyes (13.1%) were ungradable for both DR and DME and 160 (6.6%) were ungradable for DME alone. CONCLUSION: In a non-ophthalmic setting, JVN identifies the severity of DR and nondiabetic ocular conditions, permitting appropriate triage for eye care.

Adult↗
PubMed2005

A modeled economic analysis of a digital tele-ophthalmology system as used by three federal health care agencies for detecting proliferative diabetic retinopathy.

The objective of this study was to compare, using a 12-month time frame, the cost-effectiveness of a non-mydriatic digital tele-ophthalmology system (Joslin Vision Network) versus traditional clinic-based ophthalmoscopy examinations with pupil dilation to detect proliferative diabetic retinopathy and its consequences. Decision analysis techniques, including Monte Carlo simulation, were used to model the use of the Joslin Vision Network versus conventional clinic-based ophthalmoscopy among the entire diabetic populations served by the Indian Health Service, the Department of Veterans Affairs, and the active duty Department of Defense. The economic perspective analyzed was that of each federal agency. Data sources for costs and outcomes included the published literature, epidemiologic data, administrative data, market prices, and expert opinion. Outcome measures included the number of true positive cases of proliferative diabetic retinopathy detected, the number of patients treated with panretinal laser photocoagulation, and the number of cases of severe vision loss averted. In the base-case analyses, the Joslin Vision Network was the dominant strategy in all but two of the nine modeled scenarios, meaning that it was both less costly and more effective. In the active duty Department of Defense population, the Joslin Vision Network would be more effective but cost an extra 1,618 dollars per additional patient treated with panretinal laser photo-coagulation and an additional 13,748 dollars per severe vision loss event averted. Based on our economic model, the Joslin Vision Network has the potential to be more effective than clinic-based ophthalmoscopy for detecting proliferative diabetic retinopathy and averting cases of severe vision loss, and may do so at lower cost.

Cost-Benefit Analysis↗
PubMed2005

Web-based care management in patients with poorly controlled diabetes.

OBJECTIVE: To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes. RESEARCH DESIGN AND METHODS: For this study, 104 patients with diabetes and HbA(1c) (A1C) > or =9.0% who received their care at a Department of Veterans Affairs medical center were recruited. All participants completed a diabetes education class and were randomized to continue with their usual care (n = 52) or receive web-based care management (n = 52). The web-based group received a notebook computer, glucose and blood pressure monitoring devices, and access to a care management website. The website provided educational modules, accepted uploads from monitoring devices, and had an internal messaging system for patients to communicate with the care manager. RESULTS: Participants receiving web-based care management had lower A1C over 12 months (P < 0.05) when compared with education and usual care. Persistent website users had greater improvement in A1C when compared with intermittent users (-1.9 vs. -1.2%; P = 0.051) or education and usual care (-1.4%; P < 0.05). A larger number of website data uploads was associated with a larger decline in A1C (highest tertile -2.1%, lowest tertile -1.0%; P < 0.02). Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure (P < 0.01). HDL cholesterol rose and triglycerides fell in the web-based group (P < 0.05). CONCLUSIONS: Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes.

Blood Glucose↗
PubMed2005

Successfully recruiting a multicultural population: the DASH-Sodium experience.

Recruiting practices employed by the four clinical centers participating in the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial were examined to assess the most successful method of obtaining participants and to describe pertinent learning experiences gained as a result of the trial. The primary recruitment strategies employed by each center were mass mailing brochures (direct, coupon packs, or other) and mass media (advertisements in newspapers, radio, and television spots). Of 412 randomized participants, 265 (64%) were from mass distribution of brochures, 62 (15%) mass media, and 85 (21%) were prior study participants, referred by word-of-mouth, or reported coming from screening events and presentations. Although the most successful method of recruitment was mass mailing brochures, three times as many brochures were distributed to obtain similar success as in the initial DASH trial.

Adult↗
PubMed2004

Effect of dietary sodium intake on blood lipids: results from the DASH-sodium trial.

We evaluated the effect on serum lipids of sodium intake in 2 diets. Participants were randomly assigned to a typical American control diet or the Dietary Approaches to Stop Hypertension (DASH) diet, each prepared with 3 levels of sodium (targeted at 50, 100, and 150 mmol/d per 2100 kcal). The DASH diet is increased in fruits, vegetables, and low-fat dairy products and is reduced in saturated and total fat. Within assigned diet, participants ate each sodium level for 30 days. The order of sodium intake was random. Participants were 390 adults, age 22 years or older, with blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic. Serum lipids were measured at baseline and at the end of each sodium period. Within each diet, sodium intake did not significantly affect serum total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides. On the control diet, the ratio of total cholesterol-to-HDL cholesterol increased by 2% from 4.53 on higher sodium to 4.63 on lower sodium intake (P=0.04). On the DASH diet, sodium intake did not affect this ratio. There was no dose-response of sodium intake on serum lipids or the cholesterol ratio in either diet. At each sodium level, total cholesterol, LDL cholesterol, and HDL cholesterol were lower on the DASH diet versus the typical American diet. There were no significant interactions between the effects of sodium and the DASH diet on serum lipids. In conclusion, changes in dietary sodium intake over the range of 50 to 150 mmol/d did not affect blood lipid concentrations.

Adult↗
PubMed2004

Effect of the dietary approaches to stop hypertension diet and reduced sodium intake on blood pressure control.

The authors hypothesized that the Dietary Approaches to Stop Hypertension (DASH) diet and reduced sodium intake would control stage 1 hypertension and reduce high-normal blood pressure (BP) to optimal levels. Adults with systolic BP 120-159 mm Hg and diastolic BP 80-95 mm Hg were randomly assigned to receive the DASH diet or a typical American (control) diet, consuming three different sodium intakes (higher=142 mmol/d, intermediate=107 mmol/d, and lower=65 mmol/d) for 30 days each. BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Among subjects with hypertension at baseline, at higher sodium intake the DASH diet increased BP control two-fold over control (63% vs. 32%; 95% confidence interval, 1.4-2.9). Reducing sodium intake in the control diet group increased BP control 2.3-fold (74% vs. 32%; 95% confidence interval, 1.7-3.2). The maximum BP control rate (84%) was achieved with the DASH/lower sodium diet. BP became normal or optimal in 71% of persons consuming the control/lower sodium diet and 77% of persons consuming the DASH/lower sodium diet. Both the DASH diet and reduced sodium intake improved BP control.

Adult↗
PubMed2003

Effects of the Dietary Approaches to Stop Hypertension (DASH) diet on the pressure-natriuresis relationship.

Blood pressure-lowering mechanisms of the Dietary Approaches to Stop Hypertension (DASH) diet, rich in fruits, vegetables, and low-fat dairy foods, were analyzed based on the pressure-natriuresis relationship. Participants (n=375) were randomly assigned to control or DASH diet groups by using a parallel-group design. They then ate their assigned diet for 3 consecutive 30-day intervention feeding periods, during which sodium intake varied among 3 levels by a randomly assigned sequence. Urinary sodium excretion rate and mean arterial pressure were measured at the end of each sodium intake level. Mean arterial pressure and urinary sodium excretion were plotted on x and y axes, respectively, for participants eating control and DASH diets and were modeled as linear relationships for simplicity to allow the estimation of the extrapolated x-intercept and slope of the relationships. The DASH diet steepened the slope of the relationship (29.5+/-3.4 vs 64.9+/-13.1 [mmol/d]/mm Hg, P=0.0002) without significantly shifting the x-intercept (94.1+/-0.5 vs 93.2+/-0.6 mm Hg, NS) of the relationship. These data suggest a natriuretic action of the DASH diet.

Adult↗
PubMed2003

The DASH diet enhances the blood pressure response to losartan in hypertensive patients.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet, which emphasizes fruits, vegetables, and low fat dairy products, significantly lowers blood pressure (BP). We conducted a clinical trial to assess the BP response to the DASH diet with an antihypertensive medication, losartan, in participants with essential hypertension. METHODS: A total of 55 hypertensive participants were randomly assigned to 8 weeks of controlled feeding with either a control diet or the DASH diet. Within each diet arm, participants received losartan 50 mg daily or placebo for 4 weeks each, in double blind, randomized, cross-over fashion. Twenty-four-hour ambulatory BP (ABP) was measured at the end of a 2-week run-in period (baseline) and after each 4-week intervention period. RESULTS: There was no significant change in ABP during the placebo period on the control diet (n = 28) (-2.3 +/- 1.5/-1.6 +/- 1.0 mm Hg), but there was a significant reduction in systolic ABP (-5.3 +/- 1.5 mm Hg, P <.05) and no change in DBP (-2.5 +/- 1.0 mm Hg) on the DASH diet (n = 27). Losartan significantly reduced ABP on the control diet (-6.7 +/- 1.5/-3.7 +/- 1.0 mm Hg, P <.05) and to a greater extent on the DASH diet (-11.7 +/- 1.5/-6.9 +/- 1.0 mm Hg, P <.05 versus basal and control diet) particularly in African Americans. On the DASH diet, DeltaSBP on losartan was inversely related to basal plasma renin activity (n = -0.53, P =.004). CONCLUSIONS: The DASH diet enhances the ABP response to losartan in essential hypertension. This effect is particularly marked in African Americans.

Adult↗
PubMed2002

A randomized trial comparing intensive and passive education in patients with diabetes mellitus.

BACKGROUND: Patient education is a cornerstone of treatment in diabetes mellitus, but there is not unanimity of opinion as to how it should be delivered. OBJECTIVE: To determine whether a single, intensive group educational program would improve glycosylated hemoglobin (HbA(1c)) levels when compared with passive education. METHODS: A total of 106 patients with HbA(1c) levels greater than 8.5% were randomized to either an intensive (n = 50) or a passive education (n = 56) group. The intensive education group received 3.5 days of a structured curriculum involving a physician, nurse, nutritionist, pharmacist, exercise physiologist, and a social worker. The passive education group received material sent by mail every 3 months providing basic information on topics related to diabetes management. Patients continued care with their diabetes care provider during the study period. Levels of HbA(1c) were measured at baseline and 3, 6, and 12 months after randomization. A matched control group of individuals who declined participation also had HbA(1c) levels measured at baseline and 12 months. RESULTS: Mean +/- SD HbA(1c) levels fell significantly (P<.001) from baseline (9.9% +/- 1.3%) in both the intensive (-2.0%) and passive (-1.9%) education groups at 12 months, and there was no difference between the groups at any evaluation time. Both groups had significantly greater decline (P<.03) in HbA(1c) levels than a matched control group (-1.2%) with similar baseline HbA(1c) levels that did not receive education. CONCLUSIONS: Patients with elevated HbA(1c) levels who were receptive to education had substantial improvement in HbA(1c) levels after receiving an educational intervention. In this population, intensive or passive methods of delivering patient education seemed to have similar effect on improving glycemic control.

Diabetes Mellitus↗
PubMed2002

Red blood cell Na+/H+ exchange activity is insulin resistant in hypertensive patients.

A number of ion transport defects have been described in human red blood cells (RBC) from patients with essential hypertension. Insulin resistance is also frequently present in hypertensive patients and insulin levels in vitro correlate with red blood cell Na+/H+ exchange (NHE) activity. We studied the kinetics of insulin-stimulated NHE activity in freshly isolated RBC from 14 patients with essential hypertension and 8 normotensive subjects. We measured an estimate of maximal activity (Vmax) for NHE activity as net Na+ influx driven by an outward H+ gradient in acid-loaded and Na+-depleted erythrocytes. NHE activity was significantly greater in hypertensives than in normotensives (22.0 vs 14.5 mmol/L cell x h, respectively; P<0.01). When RBC were pre-incubated with a physiologic dose of insulin (100 microU/mL), NHE activity increased significantly in both groups but the increase was greater in normotensives than in hypertensives (9.6 vs 8.5 mmol/L cell x h, respectively; P < 0.05). Phosphatidylinositol-3 kinase (PI-3 kinase) inhibitors, wortmannin and LY294,002, had no effect on basal NHE activity but similarly and significantly inhibited insulin-stimulated NHE activity in both normal and hypertensive subjects. Insulin increased the Km for extracellular Na+ in normotensive subjects but not in hypertensive patients. In addition, the dose response curve for insulin and NHE activity showed that the curve for hypertensive patients was shifted rightward in relation to the normotensive subjects. These data suggest that insulin stimulates RBC NHE activity in vitro and this activation is mediated via a pathway that includes activation of PI-3 kinase. Hypertensive patients have elevated basal NHE activity but a blunted response to insulin suggesting that RBC may be a model to study insulin resistance in essential hypertensive patients.

Adult↗