MRI characteristics associated with high-grade myxoid liposarcoma.

AIM: To identify magnetic resonance imaging (MRI) features differentiating high-grade (>5% round-cell component) from low-grade myxoid liposarcomas (LPS) (≤5% round-cell component). MATERIALS AND METHODS: Informed consent was waived. Patients with myxoid LPS and MRI before biopsy, neoadjuvant therapy, and surgery were included retrospectively. High-grade components were recorded from histological specimens by a pathologist (24 years of experience). Images were evaluated by a senior radiologist (>12 years of experience) for tumour size, location, tissue layer, and MRI features (signal intensity, heterogeneity, margin, and perilesional characteristics). Descriptive statistics, Fisher's exact test to identify associations with a round-cell component, and multivariate logistic regression to identify independent predictors of high-grade tumours were used. RESULTS: Thirty-one patients (16 women [mean 51.1 years; range 19-79 years] and 15 men [mean 45.5 years; range 18-95 years]) with myxoid LPS (23 low-grade, eight high-grade) were included. All high-grade lesions had lipid signal, a peritumoural capsule and peritumoural contrast enhancement, and more commonly exhibited heterogeneous signal; however, the average size of ≥10 cm was the strongest independent indicator of high-grade status (odds ratio [OR], 14.6; 95% confidence interval [CI]: 1.6, 131). CONCLUSION: Size ≥10 cm is most strongly associated with high-grade myxoid LPS (round-cell component >5%). Other features possibly differentiating high-grade from low-grade status include lesion margin, lipid signal, and perilesional characteristics.

K4GeP4Se12: a case for phase-change nonlinear optical chalcogenide.

We report on broadband nonlinear optical (NLO) responses from a phase-change chalcogenide compound K(4)GeP(4)Se(12). Its glassy phase exhibits unusual second-harmonic generation (SHG) due to the preservation of local crystallographic order. The SHG efficiency of the glassy form can be boosted by more than 2 orders of magnitude by simple heat treatment. Strong SHG and third-harmonic generation from both glassy and crystalline compounds were characterized over a wide wavelength range of 1.2-4.0 µm. Our results imply that K(4)GeP(4)Se(12) can be utilized for various NLO applications in the mid-infrared spectrum.

Dietary calcium in human hypertension.

A pilot survey was made of the dietary calcium intake of normotensive and hypertensive individuals. Compared to 44 normotensive controls, 46 subjects with essential hypertension reported significantly less daily calcium ingestion (668 +/- 55 milligrams compared to 886 +/- 89 milligrams). The intake of other nutrients, including sodium and potassium, was very similar in the two groups. The hypertensives differed from the controls primarily in their consumption of nonfluid dairy products. The data suggest that inadequate calcium intake may be a previously unrecognized factor in the development of hypertension.

Blood pressure and nutrient intake in the United States.

A data base of the National Center for Health Statistics, Health and Nutrition Examination Survey I (HANES I), was used to perform a computer-assisted, comprehensive analysis of the relation of 17 nutrients to the blood pressure profile of adult Americans. Subjects were 10,372 individuals, 18 to 74 years of age, who denied a history of hypertension and intentional modification of their diet. Significant decreases in the consumption of calcium, potassium, vitamin A, and vitamin C were identified as the nutritional factors that distinguished hypertensive from normotensive subjects. Lower calcium intake was the most consistent factor in hypertensive individuals. Across the population, higher intakes of calcium, potassium, and sodium were associated with lower mean systolic blood pressure and lower absolute risk of hypertension. Increments of dietary calcium were also negatively correlated with body mass. Even though these correlations cannot be accepted as proof of causation, they have implications for future studies of the association of nutritional factors and dietary patterns with hypertension in America.

GATA4 sequence variants in patients with congenital heart disease.

BACKGROUND: Recent reports have identified mutations in the transcription factor GATA4 in familial cases of cardiac septal defects. The prevalence of GATA4 mutations in the population of patients with septal defects is unknown. Given that patients with septal and conotruncal defect can share a common genetic basis, it is unclear whether patients with additional types of CHD might also have GATA4 mutations. AIMS: To explore these questions by investigating a large population of 628 patients with either septal or conotruncal defects for GATA4 sequence variants. METHODS: The GATA4 coding region and exon-intron boundaries were investigated for sequence variants using denaturing high-performance liquid chromatography or conformation-sensitive gel electrophoresis. Samples showing peak or band shifts were reamplified from genomic DNA and sequenced. RESULTS: Four missense sequence variants (Gly93Ala, Gln316Glu, Ala411Val, Asp425Asn) were identified in five patients (two with atrial septal defect, two with ventricular septal defect and one with tetralogy of Fallot), which were not seen in a control population. All four affected amino acid residues are conserved across species, and two of the sequence variants lead to changes in polarity. Ten synonymous sequence variants were also identified in 18 patients, which were not seen in the control population. CONCLUSIONS: These data suggest that non-synonymous GATA4 sequence variants are found in a small percentage of patients with septal defects and are very uncommonly found in patients with conotruncal defects.

The disposal of a lime water treatment residue on soil and spoil material from a coalmine: a glasshouse investigation.

Eragrostis tef (Zucc.), Cenchrus ciliaris L., and Digitaria eriantha Steud. were grown in a soil (Psammentic Haplustalf) and spoil material from a coalmine both treated with a lime water treatment residue (WTR) at rates of 0, 50, 100, 200, and 400 g kg(-1). The yield of the grasses, from the sum of the three harvests, and concentrations of B, Ca, Cu, K, Fe, Mg, Mn, N, Na, P, and Zn in foliage from the second harvest were determined. The yield of grasses grown in the soil decreased exponentially as WTR application increased. The yields of C. ciliaris, D. eriantha, and E. tef (in the 400 g kg(-1) WTR treated soil) decreased by 74.4, 78.7, and 59.8%, respectively, when compared with the control treatments. In the spoil, the yield of E. tef and D. eriantha decreased by 13.6% and and D. eriantha by 23.9%, while an increase was observed for C. ciliaris (45.4%), at the highest WTR application rate. No relationship existed between yield of E. tef and WTR application rate when grown in the spoil, while a weak negative linear relationship (p < 0.05) was found for D. eriantha and a positive linear relationship existed for C. ciliaris. Magnesium concentrations of the grasses were positively correlated to WTR application rate. Grasses grown in the soil had higher Na concentrations, while those grown in the spoil typically had higher B, N, and Zn concentrations. The decreases in yield were attributed to nutrient deficiencies (notably Zn), induced by high WTR application rates that led to high substrate pH. Disposal of high rates of WTR on the mine materials was not recommended.

All-blood (miniplegia) versus dilute cardioplegia in experimental surgical revascularization of evolving infarction.

BACKGROUND: The advantages of blood cardioplegia include the oxygen-carrying capacity, superior oncotic and buffering properties, and endogenous antioxidants contained in blood. However, the partial dilution of blood in 4:1 (blood:crystalloid) cardioplegic solutions may nullify these advantages and progressively dilute blood during continuous retrograde delivery. This study tested the hypothesis that all-blood (66:1) cardioplegia provides superior myocardial protection compared with dilute (4:1) cardioplegia delivered in a continuous retrograde modality during surgical reperfusion of evolving myocardial infarction. METHODS AND RESULTS: After 60 minutes of left anterior descending coronary artery (LAD) occlusion, anesthetized canines were placed on cardiopulmonary bypass and randomized to either all-blood cardioplegia (AB group) or dilute blood cardioplegia (Dil group). After cross clamping, arrest was induced with 5 minutes of tepid (30 degrees C) antegrade potassium all-blood or dilute blood cardioplegia and maintained with tepid retrograde coronary sinus cardioplegia for a total of 1 hour. The LAD was released after 30 minutes of arrest, simulating revascularization. The cardioplegia hematocrit for the Dil group was lower than that for the AB group (7+/-1% versus 12+/-2%, P<0.05); at the end of bypass, systemic hematocrit was lower in the Dil group than in the Ab group (15+/-1% versus 20+/-1%, P<0.05). Infarct size (triphenyltetrazolium chloride staining) was comparable between the AB and Dil groups (29.6+/-2.9% versus 30.3+/-3.9% of area at risk), and there was no difference in area-at-risk myocardium systolic shortening (by sonomicrometry, -0.3+/-1% versus -0.4+/-1%). Tissue edema after bypass tended to be greater in the Dil group compared with the AB group in the heart (82+/-0% versus 81+/-1%), lung (79+/-1% versus 78+/-1%), liver (75+/-1% versus 74+/-0%), and skeletal muscle (76+/-1% versus 73+/-2%) and was significantly greater in the duodenum (80+/-1% versus 79+/-1%, P<0.05) and kidney (82+/-1% versus 79+/-1%, P<0.05). Postexperimental endothelial function (relaxation of acetylcholine) was impaired in LADs of the AB group versus the Dil group (59+/-6% versus 77+/-5%, P<0.05). CONCLUSIONS: Both all-blood cardioplegia and dilute cardioplegia have disadvantages, but these do not have an impact on the pathogenesis of infarct size or recovery of regional contractile function.

A population-based prospective evaluation of risk of sudden cardiac death after operation for common congenital heart defects.

OBJECTIVES: This study sought to define 1) the risk of sudden death after operation for common congenital heart defects; and 2) factors associated with an increased risk of sudden death. BACKGROUND: Although the prognosis for patients with congenital heart defects is improved by surgical treatment, they remain at a well recognized but poorly defined risk of late sudden death. METHODS: This population-based study evaluated all patients < 19 years old undergoing surgical treatment of common forms of congenital heart disease in the state of Oregon between 1958 and 1996. Patients were identified retrospectively through 1958, with prospective biannual follow-up beginning in 1982. The incidence and cause of late sudden death were evaluated for 3,589 patients surviving operation for the following defects: atrial, ventricular and atrioventricular septal defects; patent ductus arteriosus; pulmonary stenosis; aortic stenosis; coarctation of the aorta; tetralogy of Fallot; and D-transposition of the great arteries. RESULTS: There were 41 unexpected late sudden deaths during 45,857 patient-years of follow-up, an overall event rate of 1/1,118 patient-years. Thirty-seven of the 41 late sudden deaths occurred in patients with aortic stenosis, coarctation, transposition of the great arteries or tetralogy of Fallot, an event rate of 1/454 patients-years. In contrast, only four sudden deaths occurred among the other defects, an event rate of 1/7,154 patient-years (p < 0.01). The risk of late sudden death increased incrementally 20 years after operation for tetralogy of Fallot, aortic stenosis and coarctation. However, risk was not dependent on patient age at operation or surgical era. The causes of sudden death were arrhythmia in 30 patients, circulatory (embolic or aneurysm rupture) in 7 and acute heart failure in 4. CONCLUSIONS: The risk of late sudden death for patients surviving operation for common congenital heart defects is 25 to 100 times greater than an age-matched control population. This increased risk is primarily represented by patients with cyanotic or left heart obstructive lesions. The risk of sudden death appears to be time dependent, increasing primarily after the second postoperative decade.

Reproducibility of arrhythmia induction with intracardiac electrophysiologic testing: patients with clinical sustained ventricular tachyarrhythmias.

In order to characterize the day to day reproducibility of arrhythmias provoked during electrophysiologic stimulation, 114 patients with documented sustained clinical ventricular tachyarrhythmias were studied. Two baseline electrophysiologic tests were performed in the drug-free state and within 6 to 24 hours of one another. There was a significant increment (p less than or equal to 0.02) in the induction of sustained ventricular tachyarrhythmias as the number of programmed extrastimuli increased from one (10% induction) to four (64% induction). Provoked arrhythmias were observed to be more frequently nonreproducible (as reflected in a major change in rate or duration, or both, of an induced ventricular arrhythmia between baseline tests) as the number of extrastimuli increased from one (7%) to four (27%). Nonreproducibility with three and four extrastimuli was not significantly greater than when two extrastimuli were utilized. Electrophysiology-directed drug trials should be interpreted in light of this observed variability in induced arrhythmias.

Implantable cardioverter-defibrillator therapy in survivors of out-of-hospital sudden cardiac death without inducible arrhythmias.

OBJECTIVES: The aim of this study was to determine the efficacy of implantable cardioverter-defibrillator (ICD) therapy in survivors of sudden cardiac death in whom no ventricular arrhythmias can be induced with programmed electrical stimulation. BACKGROUND: Survivors of sudden cardiac death in whom ventricular arrhythmias cannot be induced with programmed electrical stimulation remain at risk for recurrence of serious arrhythmias. Optimal protection to prevent sudden death in these patients is uncertain. This study compares survival in the subset of survivors of sudden cardiac death with that of patients treated with or without an ICD. METHODS: A retrospective study was performed on 194 consecutive survivors of primary sudden death who had < or = 6 beats of ventricular tachycardia induced with programmed electrical stimulation with at least three extrastimuli. Ninety-nine patients received an ICD and 95 did not. RESULTS: There were no significant differences between the two groups in presenting rhythm, number of prior myocardial infarctions or use of antiarrhythmic agents. Patients treated with an ICD were younger (55 +/- 16 vs. 59 +/- 11 years, p = 0.03) and had a lesser incidence of coronary artery disease (48% vs. 63%, p = 0.04) and a lower ejection fraction (0.43 +/- 0.16 vs. 0.48 +/- 0.18, p = 0.04). There were no significant differences between the groups in the use of revascularization procedures or antiarrhythmic agents after the sudden cardiac death. Patients treated with an ICD had an improvement in sudden cardiac death-free survival (p = 0.04) but the overall survival rate did not differ from that of the patients not so treated (p = 0.91). A multivariate regression analysis that adjusted for the observed differences between the groups did not alter these results. CONCLUSIONS: Survivors of sudden cardiac death in whom no arrhythmias could be induced with programmed electrical stimulation remained at risk for arrhythmia recurrence. Although the proportion of deaths attributed to arrhythmias was lower in the patients treated with an ICD, this therapy did not significantly improve overall survival.

Acetabular development after bipolar hemiarthroplasty for osteosarcoma in children.

A retrospective analysis was performed of eight patients with an open triradiate cartilage, who underwent resection for osteosarcoma and reconstruction of the proximal femur with a hemiarthroplasty, in order to identify changes of acetabular development. An analysis of the centre-edge angle, teardrop-to-medial prosthesis distance, superior joint space, teardrop-to-superior prosthesis distance, degree of lateral translation, and arthritic changes, was performed on serial radiographs. The median age at the time of the initial surgery was 11 years (5 to 14). All patients developed progressive superior and lateral migration of the prosthetic femoral head. Following hemiarthroplasty in the immature acetabulum, the normal deepening and enlargement of the acetabulum is arrested. The degree of superior and lateral migration of the prosthetic head depends on the age at diagnosis and the length of follow-up.

Nutritional management of cardiovascular risk factors. A randomized clinical trial.

BACKGROUND: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. OBJECTIVE: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. METHODS: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. RESULTS: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean differences (+/-SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-group P values), respectively, were as follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02); diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, -0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/- 21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/- 0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg; and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly improved for daily and work activities (P < .05) and nutritional health perceptions (P < .05) with the CCNW plan relative to the self-selected group. Overall nutrient intake and compliance were both significantly (P < .001) better with the CCNW plan. CONCLUSIONS: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease.

A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction.

OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons. DESIGN: In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN OUTCOME MEASURES: The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.

Multicenter randomized trial of a comprehensive prepared meal program in type 2 diabetes.

OBJECTIVE: To evaluate the clinical effects of a comprehensive prepackaged meal plan, incorporating the overall dietary guidelines of the American Diabetes Association and other national health organizations, relative to those of a self-selected diet based on exchange lists in free-living individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 202 women and men (BMI < or = 42 kg/m2) whose diabetes was treated with diet alone or an oral hypoglycemic agent were enrolled at 10 medical centers. After a 4-week baseline period, participants were randomized to a nutrient-fortified prepared meal plan or a self-selected exchange-list diet for 10 weeks. On a caloric basis, both interventions were designed to provide 55-60% carbohydrate, 20-30% fat, and 15-20% protein. At intervals, 3-day food records were completed, and body weight, glycemic control, plasma lipids, and blood pressure were assessed. RESULTS: Food records showed that multiple nutritional improvements were achieved with both diet plans. There were significant overall reductions in body weight and BMI, fasting plasma glucose and serum insulin, fructosamine, HbA1c, total and LDL cholesterol, and blood pressure (P < 0.001 or better for all). In general, differences in major end points between the diet plans were not statistically significant. CONCLUSIONS: Glycemic control and cardiovascular risk factors improve in individuals with type 2 diabetes who consume diets in accordance with the American Diabetes Association guidelines. The prepared meal program was as clinically effective as the exchange-list diet. The prepared meal plan has the additional advantages of being easily prescribed and eliminating the complexities of meeting the multiple dietary recommendations for type 2 diabetes management.

Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion.

OBJECTIVE: The purpose of this study was to compare protective effects of AMP579 and adenosine (Ado) at reperfusion (R) on inhibition of polymorphonuclear neutrophil (PMN) activation, PMN-mediated injury to coronary artery endothelium, and final infarct size. METHODS: In anesthetized dogs, 1 h of left anterior descending coronary artery occlusion was followed by 24 h R and drugs were administered at R. Control (n=8, saline control), AMPI (n=7, AMP579, 50 microg/kg i.v. bolus followed by 3 microg/kg/min for 2 h), AMPII (n=7, AMP579, 50 microg/kg i.v. bolus), AMPIII (n=7, AMP579, 3 microg/kg/min i.v. for 2 h), and Ado (n=7, adenosine, 140 microg/kg/min i.v. for 2 h). RESULTS: AMP579 in vitro directly inhibited superoxide radical (O(-)(2)) generation (nM/5x10(6) PMNs) from PMNs dose-dependently (from 17+/-1* at 10 nM to 2+/-0.2* at 10 microM vs. activated 30+/-2). However, inhibition of O(-)(2) generation by Ado at each concentration was significantly less than for AMP579. The IC(50) value for AMP579 (0.09+/-0.02 microM) on O(-)(2) generation was significantly less than that of Ado (3.9+/-1. 1 microM). Adherence of unstimulated PMN to postischemic coronary artery endothelium (PMNs/mm(2)) was attenuated in AMPI and AMPIII vs. Control (60+/-3* and 58+/-3* vs. Control 110+/-4), while Ado partially attenuated PMN adherence (98+/-3*). Accordingly, endothelial-dependent vascular relaxation was significantly greater in AMPI and AMPIII vs. Ado. At 24 h R, myocardial blood flow (MBF, ml/min/g) in the area at risk (AAR), confirmed by colored microspheres, in AMPI and AMPIII was significantly improved (0.8+/-0. 1* and 0.7+/-0.1* vs. Control 0.3+/-0.04). Infarct size (IS, TTC staining) in AMPI and AMPIII was significantly reduced from 38+/-3% in Control to 21+/-4%* and 22+/-3%*, respectively, confirmed by lower plasma creatine kinase activity (I.U./g protein) in these two groups (27+/-6* and 32+/-2* vs. 49+/-3). Cardiac myeloperoxidase activity (MPO, Abs/min) in the AAR was significantly reduced in AMPI and AMPIII vs. Control (36+/-11* and 35+/-10* vs. 89+/-10). However, changes in MBF, IS and MPO were not significantly altered by Ado. CONCLUSIONS: These data suggest that continuous infusion of AMP579 at R is more potent than adenosine in attenuating R injury, and AMP579-induced cardioprotection involves inhibition of PMN-induced vascular and myocardial tissue injury. *P<0.05 vs. Control.

Human nutrition and blood pressure regulation: an integrated approach.

This review highlights the complex interactions that constitute the disciplines of nutrition and cardiovascular physiology. Nutritional factors have long been considered as critical in the pathogenesis of human hypertension. Theoretical and established contributions of various nutrients to blood pressure regulation are presented. A brief historical perspective of sodium's dominance in this area is provided. "Accepted" principles of nutrient interaction are then applied to cardiovascular research. First, the interrelationships among all macronutrients and diet composition, nutrient absorption, renal elimination, and ultimate bioavailability to the vascular tissue are assessed. An analysis of dietary recall data from human studies is provided to illustrate such nutrient interaction. Second, associated factors that influence nutrition are considered in relation to both human and animal investigations of blood pressure regulation. Finally, the development and interpretation of future studies are assessed in light of these principles. Examples from both the human and animal investigations of blood pressure regulation. Finally, the development and interpretation of future studies are assessed in light of these principles. Examples from both the human and animal literature are provided to show why it is necessary to incorporate fully the established principles of nutrition into our current concepts of the pathogenesis of hypertension. Future progress in terms of nutrition, food, and health will be dependent upon such an integrated approach.

Decreased calcium pump adenosine triphosphatase in red blood cells of hypertensive subjects.

Several operationally defined adenosine triphosphatase (ATPase) activities were determined in vitro in red blood cell lysates of normotensive or hypertensive humans: Mg2+-ATPase, Na+,K+-ATPase, and Ca2+ pump ATPase, the latter in the calmodulin-activated and basal states. Basal Ca2+ pump ATPase was defined as the Ca2+-activated ATPase resistant to 10(-4) M trifluoperazine. Subjects were part of a double-blind study in which treatment was divided into several phases: baseline (4 weeks), placebo or calcium (1 g elemental calcium/day, 8 weeks), placebo washout (4 weeks), placebo or calcium (1 g elemental calcium/day, 8 weeks). Irrespective of the phase of treatment, the basal Ca2+ pump ATPase activity in red blood cell lysates of 36 hypertensive subjects was significantly less than that in lysates from 18 normotensive subjects. Other ATPase activities did not differ significantly, although all ATPases tended to be decreased in hypertension. The data are consistent with previous reports of altered membrane Ca2+ binding and transport in hypertension, but the precise changes are not elucidated.

Effect of dietary sodium restriction on overall nutrient intake.

Sodium restriction, widely prescribed for hypertensive persons and recommended for the broader US population, may result in nutrient alterations that could either beneficially or detrimentally affect overall diet quality. Most dietary sodium comes from meats (including poultry and fish), grains, and dairy products. These three groups also provide most dietary calcium, iron, magnesium, and vitamin B-6. Thus, reduced consumption of foods that are primary sodium sources could concurrently reduce the dietary content of these other nutrients below recommended daily intakes. This consequence of sodium restriction has not been specifically addressed in clinical trials. Although intake of most food groups was significantly reduced by a sodium-restricted diet in the Hypertension Prevention Trial, three other large clinical trials reported differing effects of sodium restriction on simultaneous energy and nutrient intakes. In the largest study of the effects of a sodium-restricted diet on intake of all major nutrients, sodium reduction was accompanied by lower energy intake and, concomitantly, lower intakes of total fat, saturated fat, protein, carbohydrate, and calcium. Present data are inadequate for determining the potential nutrient alterations of a broad prescription of sodium restriction. Difficulties in interpreting the available data result from the combination of sodium restriction with other interventions, intensive sodium reduction measures that do not reflect clinical implementation, poor compliance with sodium restriction, lack of analysis of changes in patterns of food intake, and interventions that are too short to reflect stable dietary patterns.

Plasma lipids and hypertension: response to calcium supplementation.

Evidence from animal and human studies indicate that calcium supplementation may ameliorate two risk factors for atherosclerotic cardiovascular disease, hypertension and hyperlipidemia. We sought to characterize dietary fat consumption and plasma lipid profiles in hypertensive and normotensive subjects and plasma lipid responses to supplemental calcium. A randomized, double-blind, placebo-controlled, crossover protocol was used to assess blood pressure and lipid response to 8 wk of 1000 mg of elemental calcium in 43 hypertensive and 27 normotensive subjects. Nutrient intakes and plasma lipids were measured repeatedly. Hypertensive female subjects consumed significantly less (p less than 0.05) phosphorus, potassium, and magnesium and had significantly higher triglycerides (p less than 0.04) and lower HDL-cholesterol (p less than 0.02) than did normotensive subjects. There were no significant changes in dietary plasma lipids with calcium supplementation. Mildly hyperlipidemic normotensive subjects had a significant decrease in total cholesterol (p less than 0.05). No significant changes in plasma lipids occurred with calcium supplementation in hypertensive subjects.

Compliance to a low-salt diet.

Community intervention projects, efforts at single centers, and multicenter, prospective, dietary salt-restriction trials suggest that such an intervention is neither easy to achieve nor simple to maintain. Community-wide interventions based on advertisements, pamphlets, posters, radio messages, instructions in schools or other institutions, and cooperation from food suppliers such as butchers and bakers resulted in a slight decrease in salt consumption, mostly in normotensive women. A demonstration project at a single center showed that lowering salt intake long-term by 50% in hypertensive patients was feasible. That study included self-administered, positive-feedback devices to indicate adherence and a role for a household partner in achieving compliance. Multicenter intervention trials also indicate that reducing salt intake in the long term is feasible. However, in all intervention trials the subjects were highly selected, stable, generally married male volunteers. An elaborate training program involving many health care professionals was necessary and recidivism was common. Successful intervention requires specific goals and delegated responsibilities on the part of the health care team, careful assessment of the patient and the risk factors, as well as motivation for behavioral change, a specific plan for implementation, repetitive educational efforts, and a built-in monitoring mechanism.