A computational study of functional endoscopic sinus surgery and maxillary sinus drug delivery.

BACKGROUND: Topical medication is increasingly used following functional endoscopic sinus surgery (FESS). Information on particle sizes that maximise maxillary sinus (MS) delivery is conflicting, and the effect of antrostomy size on delivery is unclear. The purpose of this study was to estimate antrostomy and particle size effects on topical MS drug delivery. METHODOLOGY: Sinonasal reconstructions were created from a pre- and a post-FESS CT scan in each of four chronic rhinosinusitis patients. Additional models were created from each post-FESS reconstruction representing four alternative antrostomy sizes. Airflow and particle deposition were simulated in each reconstruction using computational fluid dynamics for nebulised and sprayed delivery. RESULTS: MS ventilation and drug delivery increased following FESS, the largest virtual antrostomy led to greatest delivery, and MS delivery was sensitive to particle size. Particles within a 5-18 µm and 5-20 µm size range led to peak MS deposition for nebulised and sprayed particles, respectively. Post-FESS increases in drug delivery varied across individuals and within individuals by the type of antrostomy created. CONCLUSION: Our findings suggest that FESS, particularly with larger antrostomies, improves topical drug delivery, and that certain particle sizes improve this delivery. Further research is needed to contextualise these findings with other post-surgical effects.

Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.

The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and nine lean patients with a BMI < or =25 kg/m2 (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the alpha-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02) and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/-1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

The effect of weight loss intervention on antihypertensive medication requirements in the hypertension Optimal Treatment (HOT) study.

Obesity is a significant risk factor for hypertension and the cardiovascular sequelae of hypertension. Weight loss has been shown to be effective in lowering blood pressure in overweight individuals. The purpose of this study was to show the impact of a weight loss intervention on overall medication requirements for obese, hypertensive patients. This was a substudy of the Hypertension Optimal Treatment (HOT) study. HOT study patients who had a body mass index > or =27 kg/m2 were randomized to receive either the weight loss intervention, which included dietary counseling and group support, or to serve as the control group. Patients' weights and number of medication steps (per HOT protocol) required to achieve target diastolic blood pressure were measured at 3, 6, 12, 18, 24, and 30 months. Patients in the weight loss group lost significantly more weight than the control group only at 6 months (-3.2+/-4.3 v. -1.8+/-2.7 kg [mean +/- SD] for weight loss group versus control, respectively, P = .05). The weight loss group tended to regain weight after the first 6 months of the study. However, patients in the weight loss group used a significantly fewer number of medication steps than the control group at all time intervals except 3 months. Weight loss appears to be a useful tool in blood pressure management in patients who require medication to control their blood pressure.

Therapeutic considerations in the treatment of obesity hypertension.

Obesity, now recognized as an independent risk factor for cardiovascular disease, is closely associated with hypertension. Complex mechanisms link increasing body weight with increasing blood pressure. Treatment of the obese patient with hypertension requires consideration of physiologic changes related to obesity hypertension. Lifestyle modification, including weight reduction and increased physical activity, can directly influence blood pressure levels and improve blood pressure control in obese, hypertensive patients. Clinical trials are needed to determine the most effective antihypertensive drugs for the obese, hypertensive patient. Antiobesity drugs offer viable adjunctive pharmacotherapy for obesity hypertension, but additional long-term studies are needed to support their safety and efficacy.

Effect of soybean protein on novel cardiovascular disease risk factors: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of death in the United States and the world. Clinical trials have suggested that soybean protein lowers lipids and blood pressure. The effect of soybean protein on novel CVD risk factors has not been well studied. The objective of this study was to examine the effect of soybean protein on biomarkers of inflammation, endothelial dysfunction and adipocytokines. SUBJECTS/METHODS: The effect of 8 weeks of 40 g of soybean protein supplement (89.3 mg isoflavones), 40 g of milk protein supplement and 40 g of complex carbohydrate placebo was examined in a randomized, placebo-controlled, double-blind, three-phase crossover trial among adults in New Orleans, Louisiana and Jackson, Mississippi. Plasma levels of inflammation biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-α), endothelial dysfunction biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, thrombomodulin) and adipocytokines (high-molecular weight adiponectin, leptin, resistin) were measured at baseline and at the end of each intervention using immunoturbidimetric and enzyme-linked immunosorbent assay techniques. RESULTS: Soy protein supplementation resulted in a significant mean net change (95% confidence interval) in plasma E-selectin of -3.93 ng/ml (-7.05 to -0.81 ng/ml; P=0.014) compared with milk protein, and in plasma leptin of -2089.8 pg/ml (-3689.3 to -490.3 pg/ml; P=0.011) compared with carbohydrate. There were no significant changes in any other risk factors. CONCLUSIONS: Soy protein supplementation may reduce levels of E-selectin and leptin. Further research is warranted to investigate the mechanisms through which protein may confer protective effects on novel CVD risk factors.

Effect of soy and milk protein supplementation on serum lipid levels: a randomized controlled trial.

BACKGROUND/OBJECTIVE: Previous clinical trials have documented that soy protein reduces low-density lipoprotein cholesterol and increases high-density lipoprotein (HDL) cholesterol compared with milk protein. However, the effect of soy protein on lipids compared with carbohydrate has not been not well studied. We examined the effect of soy and milk protein supplementation on lipids and lipoproteins compared with carbohydrate among adults without hypercholesterolemia. SUBJECTS/METHODS: We conducted a randomized, double-blind, 3-phase crossover trial among 352 US adults with serum total cholesterol level of <240 mg/dl from September 2003 to April 2008. Trial participants were assigned to 40 g/day supplementation of soy protein, milk protein or complex carbohydrate from wheat each for 8 weeks in random order with a 3-week washout period between interventions. Overnight fasting blood samples were collected at the termination of each intervention phase. RESULTS: Compared with carbohydrate, soy protein supplementation was significantly associated with a net change (95% confidence interval (CI)) in total cholesterol and total/HDL cholesterol ratio of -3.97 mg/dl (-7.63 to -0.31, P=0.03) and -0.12 (-0.23 to -0.01, P=0.03), respectively. Compared with milk protein, soy protein supplementation was significantly associated with a net change (95% CI) in HDL and total/HDL cholesterol ratio of 1.54 mg/dl (0.63 to 2.44, P=0.0009) and -0.14 (-0.22 to -0.05, P=0.001), respectively. Compared with carbohydrate, milk protein supplementation was significantly associated with a net change (95% CI) in HDL of -1.13 mg/dl (-2.05 to -0.22, P=0.02). CONCLUSIONS: This randomized controlled trial indicates that soy protein, but not milk protein, supplementation improves the lipid profile among healthy individuals.

Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study.

BACKGROUND: Previous research has suggested that thiazide diuretics and beta-blockers may promote the development of type 2 diabetes mellitus. However, the results of previous studies have been inconsistent, and many studies have been limited by inadequate data on outcomes and by potential confounding. METHODS: We conducted a prospective study of 12,550 adults 45 to 64 years old who did not have diabetes. An extensive health evaluation conducted at base line included assessment of medication use and measurement of blood pressure with a random-zero sphygmomanometer. The incidence of new cases of diabetes was assessed after three years and after six years by measurement of serum glucose concentrations while the subjects were fasting. RESULTS: After simultaneous adjustment for age, sex, race, education, adiposity, family history with respect to diabetes, physical-activity level, other health-related behavior, and coexisting illnesses, subjects with hypertension who were taking thiazide diuretics were not at greater risk for the subsequent development of diabetes than were subjects with hypertension who were not receiving any antihypertensive therapy (relative hazard, 0.91; 95 percent confidence interval, 0.73 to 1.13). Likewise, subjects who were taking angiotensin-converting-enzyme inhibitors and calcium-channel antagonists were not at greater risk than those not taking any medication. In contrast, subjects with hypertension who were taking beta-blockers had a 28 percent higher risk of subsequent diabetes (relative hazard, 1.28; 95 percent confidence interval, 1.04 to 1.57). CONCLUSIONS: Concern about the risk of diabetes should not discourage physicians from prescribing thiazide diuretics to nondiabetic adults who have hypertension. The use of beta-blockers appears to increase the risk of diabetes, but this adverse effect must be weighed against the proven benefits of beta-blockers in reducing the risk of cardiovascular events.

Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. METHODS: A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. FINDINGS: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. INTERPRETATION: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.