Health services utilization, satisfaction, and attachment to a regular source of care among participants in an urban health provider alliance.

This study examines the effect of a provider alliance on service utilization, satisfaction , self efficacy, and attachment to a regular source of care for participating low income urban children and their families. The use of Physician Assistants and community health workers to expand community outreach, primary care services, pediatric sub-specialty care, and service coordination within and between care settings improved health services utilization, satisfaction with health services, parental self efficacy in navigating the health care system for their children, and service convenience for an at-risk population. Also, the use of Physician Assistants to provide pediatric sub-specialty services did not have a negative effect on parental satisfaction with a child's care. Parents were slightly more satisfied with services received from a Physician Assistant in comparison with the physician sub- specialists in cardiology and nephrology clinics.

Sirtuin 6 (SIRT6) regulates redox homeostasis and signaling events in human articular chondrocytes.

The nuclear localized protein deacetylase, SIRT6, has been identified as a crucial regulator of biological processes that drive aging. Among these processes, SIRT6 can promote resistance to oxidative stress conditions, but the precise mechanisms remain unclear. The objectives of this study were to examine the regulation of SIRT6 activity by age and oxidative stress and define the role of SIRT6 in maintaining redox homeostasis in articular chondrocytes. Although SIRT6 levels did not change with age, SIRT6 activity was significantly reduced in chondrocytes isolated from older adults. Using dimedone-based chemical probes that detect oxidized cysteines, we identified that SIRT6 is oxidized in response to oxidative stress conditions, an effect that was associated with reduced SIRT6 activity. Enhancement of SIRT6 activity through adenoviral SIRT6 overexpression specifically increased the basal levels of two antioxidant proteins, peroxiredoxin 1 (Prx1) and sulfiredoxin (Srx) and decreased the levels of an inhibitor of antioxidant activity, thioredoxin interacting protein (TXNIP). Conversely, in chondrocytes derived from mice with cartilage specific Sirt6 knockout, Sirt6 loss decreased Prx1 levels and increased TXNIP levels. SIRT6 overexpression decreased nuclear-generated H2O2 levels and oxidative stress-induced accumulation of nuclear phosphorylated p65. Our data demonstrate that SIRT6 activity is altered with age and oxidative stress conditions associated with aging. SIRT6 contributes to chondrocyte redox homeostasis by regulating specific members of the Prx catalytic cycle. Targeted therapies aimed at preventing the age-related decline in SIRT6 activity may represent a novel strategy to maintain redox balance in joint tissues and decrease catabolic signaling events implicated in osteoarthritis (OA).

Comparison of the cardiac output and stroke volume response to upright exercise in children with valvular and subvalvular aortic stenosis.

Cardiac output and stroke volume were evaluated in 17 children (mean age 11.5 +/- 3 years) with discrete, membranous subvalvular (Group I, n = 7) and valvular (Group II, n = 10) aortic stenosis during submaximal and maximal (greater than 75% predicted maximal oxygen consumption) upright cycle ergometry. Patients with valvular aortic stenosis were further subdivided on the basis of their aortic valve gradient at rest determined by cardiac catheterization (Group IIA, gradient less than 40 mm Hg; Group IIB, gradient greater than or equal to 40 mm Hg). These patients were matched with 17 control subjects on the basis of age, sex, height and intensity of exercise during maximal exertion. Cardiac and stroke indexes were determined by the acetylene rebreathing method at each exercise level. Stroke volume index in Group I was significantly greater at rest when compared with that in control subjects (69 +/- 13 versus 53 +/- 11 ml/m2, alpha = 0.01, p less than 0.05) and that in patients in Group II (69 +/- 13 versus 47 +/- 12 ml/m2, alpha = 0.01, p less than 0.05). Patients with subvalvular aortic stenosis were unable to increase their stroke volume index from rest to submaximal exercise and also decreased their stroke volume index at maximal exercise levels. In contrast, patients with mild valvular aortic stenosis (Group IIA) displayed a normal exercise response. Patients with severe valvular aortic stenosis (Group IIB) had a blunted stroke volume response at rest and at each level of exercise, as well as signs of myocardial ischemia (ST segment depression) during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exercise training on insulin sensitivity in adolescents with type I diabetes.

We investigated the influence of a program of exercise training consisting of three weekly sessions, each 45 min long, for 12 wk, on indices of physical fitness, glycemic control, and insulin sensitivity in nine adolescents with type I diabetes; six age-matched adolescents with diabetes of equivalent duration served as nonexercised controls. All subjects were instructed not to change dialy insulin dose or caloric intake. In the exercised group, maximal oxygen uptake during graded cycle ergometry to volitional exhaustion increased by 9 +/- 2.7% (P less than 0.01) and lean body mass increased by 4 +/- 1.8% (P less than 0.05). Insulin sensitivity, assessed via the euglycemic clamp technique at insulin infusion rates of 100 mU/M2/min, showed an increase of insulin-mediated glucose disposal from 274 +/- 33 to 338 +/- 28 mg/M2/min, representing an increase in insulin sensitivity of 23 +/- 5% (P less than 0.01). None of these indices changed in the control group. Despite increased insulin sensitivity, glycohemoglobin levels remained at 12 +/- 1% before and after the 12 wk of exercise training, indicating no improvement in overall glycemic control. No increase in hypoglycemic reactions was reported in either group. We conclude that exercise training may be a valuable adjunct in managing type I diabetes providing there is concomitant attention to diet and insulin. Exercise training alone, however, does not improve glycemic control, although it improves physical fitness and insulin sensitivity.

Maximal exercise stress testing in normal and hyperlipidemic children.

Electrocardiographic and cardiovascular responses during maximal exercise were evaluated in 103 normal children and in 82 children with familial hyperlipoproteinemia. The normal and hyperlipidemic children were comparable in regards to age, weight--height index, resting and exercise blood pressures, and maximal working capacity indices. The cohort of 82 hyperlipidemic children included 61 children (29 boys and 32 girls) with well defined "monogenic" familial hyperlipoproteinemia. Segmental ST depression on the exercise electrocardiogram occurred in 8 of these 29 boys (27.6%) as compared to 4 of 55 normal boys (7.3%), P less than 0.025 and in 6 of the 32 girls (19%) as compared to 7 of 48 normal girls (14.6%), P greater than 0.1. Segmental ST depression was present in 14 of 61 (23%) children with "monogenic" hyperlipoproteinemia, as compared to 11 of 103 (10.75%) normal (x2 = 4.47, P less than 0.05). An assessment of the clinical significance of an abnormal exercise electrocardiogram in male children with "monogenic" hyperlipoproteinemia must await the following: (1) two to four decades of observation and study of the development of morbid or mortal coronary disease, or (2) the future development of improved invasive or noninvasive techniques for the early detection of covert coronary occlusive disease. Currently, maximal exercise electrocardiography cannot be contemplated as a useful indicator of eventual premature coronary artery disease in asymptomatic hyperlipidemic children.

Exercise electrocardiogram, blood pressure, and working capacity in young patients with valvular or discrete subvalvular aortic stenosis.

Electrocardiographic changes, blood pressure, and working capacity (total work) were recorded during an upright cycle exercise test in 65 children and young adults (mean age 12 years) with valvular or discrete subvalvular aortic stenosis. All patients had cardiac catheterization, but none had surgical treatment. Controls consisted of 164 normal subjects (mean age 15 years). In the patients, the intervals between the exercise test and cardiac catheterization were 1 month or less in 66%, 2 to 12 months in 28%, and 12 to 24 months in 6%. The patients were classified by resting left ventricular to aortic peak systolic pressure gradient into Groups I (gradient less than 30 mm Hg), II (30 to 49 mm Hg), III (50 to 69 mm Hg), and IV (70 mm Hg or greater). The mean frequency and magnitude of exercise-induced S-T depression were greater in the patients than in the control subjects (p less than 0.005) and increased with increasing obstruction in the patients. Mean total work and peak exercise systolic pressure were significantly decreased in the patients with a left ventricular to aortic systolic gradient of 30 mm Hg or greater as compared with the control subjects (p less than 0.03). An exercise profile consisting of S-T depression of 2 mm or more, and markedly decreased total work and systolic blood pressure were characteristic of the 19 patients (Group IV) with a resting left ventricular to aortic systolic gradient of 70 mm Hg or greater. At least 2 or more components of this exercise profile occurred in 11 (24%) of the 46 patients with a resting left ventricular to aortic systolic gradient less than 70 mm Hg. This study demonstrates that exercise testing reveals serious abnormalities in patients otherwise classified as having trivial or moderate obstruction, and that a properly performed exercise study can be done at minimal risk to the patient.

Aortic valve replacement in childhood: evaluation of left ventricular function by electrocardiography, echocardiography and graded exercise testing.

Preoperative and postoperative left ventricular (LV) performance was evaluated noninvasively in 15 children who survived aortic valve replacement (AVR). The noninvasive evaluation included electrocardiography, M-mode echocardiography, and graded exercise testing. Clinically, there was dramatic improvement postoperatively: All but 2 patients were asymptomatic. No conduction defects or arrhythmias were detected preoperatively; however, in the late postoperative period there was a variety of intraventricular conduction abnormalities, myocardial infarctions, and ventricular or supraventricular arrhythmias. On M-mode echocardiography, children with aortic stenosis continued to have increased LV mass postoperatively. Shortening fraction and left-sided systolic time intervals returned to normal. The children with aortic regurgitation also had persistently abnormal LV mass on echocardiography postoperatively. Exercise data indicated no improvement in working capacity after AVR. Also, 9 children (63%) continued to have ST-segment depression with maximal exercise. These data indicate that AVR does not result in a return to normal of myocardial performance in children with severe aortic valve disease.

Azelastine effects on electrical and mechanical activities of guinea pig papillary muscles.

The effects of azelastine, a new anti-asthmatic drug under clinical investigation, were studied on both normal fast action potentials (APs) and slow APs using conventional microelectrode techniques in guinea pig papillary muscles (superfused with oxygenated Tyrode solution at 37 degrees C). Slow APs were induced by either 10(-7) M isoproterenol, 10(-5) M histamine, db-cAMP (3 mM) or 10 mM TEA, in the presence of 25 mM [K]o to voltage inactive the fast Na+ channels. At 10(-5) M, azelastine depressed the maximum rate of rise (+Vmax) of the slow APs and the force of contraction. At 3 X 10(-5) M, azelastine further reduced +Vmax and the amplitude of the slow APs; complete abolishing of slow APs and contractions occurred at 10(-4) M. Upon washout of the drug, automaticity appeared. In the presence of 10(-4) M azelastine, increasing the [Ca]o concentration from 1.8 to 3.6 and 5.4 mM caused partial recovery of the slow APs and contractions. The fast APs were also depressed by azelastine. At 10(-5) and 3 X 10(-5) M, azelastine reduced +Vmax and the AP duration at 50% repolarization (APD50) of the fast APs. Complete block of the fast APs and suppression of contractions were observed after 30 min at 10(-4) M azelastine. After 3-5 h of washout, excitability recovered; however, +Vmax was depressed and APD90 was prolonged. It is concluded that azelastine inhibits the slow Ca2+ channels and the fast Na+ channels. The slow recovery suggests that the drug may accumulate inside the cells, and exert a prolonged inhibitory effect on contraction.

Cardiac performance in children with pectus excavatum.

Fourteen children with pectus excavatum and 14 normal control patients underwent graded exercise testing using a cycle ergometer and the James protocol. All the subjects were preoperative. The children were exercised to exhaustion during the test. The pectus and control groups were broken down into subgroups consisting of subjects less than or equal to 10 years of age and subjects greater than or equal to 11 years of age (pectus and controls less than or equal to 10 years old, PI and CI, respectively; pectus and controls greater than or equal to 11 years old, PII and CII, respectively). Maximal workload, oxygen consumption, cardiac output, and stroke volume were not significantly different when comparing the total groups or when each of the respective subgroups were compared. However, maximal diastolic BP was significantly elevated when the entire pectus and control groups were compared. When the subgroups were compared, maximal diastolic BP was elevated only in the older pectus patients (PII) and remained so until five minutes after exercise. Additionally, left ventricular systolic time intervals were measured immediately after exercise in all the children. The ratio of preejection period to left ventricular ejection time (P/L) was significantly shortened in the total pectus group. When the subgroups were compared, the P/L ratio was significantly decreased only in the older patients. Also, the preejection period (PEP) was significantly shortened in the older pectus patients. It appears that children with pectus excavatum have a normal exercise tolerance and oxygen transport. However, older pectus children develop an increased diastolic BP and a shortened P/L and PEP in response to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Physical Training on Blood Lipid Profiles in Adolescents With Insulin-Dependent Diabetes Mellitus.

In brief: Fourteen adolescents (eight females and six males) with insulin-dependent diabetes mellitus (IDDM) participated in a 12-week exercise program consisting of three 45-minute sessions per week. Exercise consisted of calisthenic warm-up and stretching (ten minutes), aerobic movement to music (25 minutes at 80% V o2 max), and cool-down (ten minutes). The purpose was to determine whether and to what degree such training would bring about changes in blood lipid and lipoprotein profiles in such patients. The authors found a significant decrease in low-density lipoprotein cholesterol concomitant to an increase in V o2 max with no change in glycemic control. These findings support the beneficial effects of regular exercise for individuals with IDDM.

Exercise testing in children and young adults: an overview.

This chapter has demonstrated the diagnostic capability and feasibility of documenting functional abnormalities during dynamic stress in a pediatric population. The overview confirms that a controlled exercise procedure can be performed routinely in ambulatory children with or without cardiovascular disease and should be included in the clinical evaluation of specific lesions. It now appears that the primary indications for noninvasive exercise testing in the pediatric population include the following disorders: 1. Left ventricular outflow obstructions, a. Subvalvar obstructions, b. Valvar obstructions, c. Supravalvar obstructions, d. Idiopathic hypertrophic subaortic stenosis, e. Coarctation of the aorta; 2. Chronic left or right ventricular volume overload, a. Atrioventricular or semilunar valve incompetence, b. Left-to-right shunts; 3. Rhythm and conduction disturbances, a. Postoperative ventriculotomy, b. Bradytachyarrhythmias, c. Arrhythmias in patients with or without symptoms. The role of the exercise procedure is not yet established in the following areas: 1. Patients with family history of premature atherosclerosis or Type II hyperlipoproteinemia; 2. Patients with elevated blood pressure; 3. The evaluation of syncope, chest pain, or atypical findings on physical examinations (especially in athletes). Consequent upon increased interest and improved technology, the role of this technique will soon be established in the invasive and noninvasive evaluation of pediatric patients with or without overt cardiovascular disease.

Unexpected cardiac arrest in patients after surgical correction of tetralogy of Fallot.

Four of 220 patients without bifasicular block (complete right bundle branch block and left anterior hemiblock) or transient complete heart block immediately after surgery had an unexpected cardiac arrest one to 15 years after satisfactory surgical repair of tetralogy of Fallot. The postoperative electrocardiograms (ECG) revealed complete right bundle branch block in two patients and no intraventricle conduction abnormality in two patients. Each of the four patients had premature ventricular contractions on previous postoperative ECG. The cardiac arrest occurred during normal activity in three patients and mild exercise in one. Following the cardiac arrest, three patients died and one patient survived. Eighteen months before the cardiac arrest, the survivor had a stress test which revealed multifocal premature ventricular contractions with short bursts of ventricular tachycardia after exercise. This ventricular arrhythmia was suppressed with quinidine therapy. Although complete heart block cannot be excluded in these four patients, we reasoned that the cardiac arrests were probably preceded by ventricular tachyarrhythmia. Because of this experience, we believe that any patient who has had intraventricular surgery should be evaluated for ventricular arrhythmia. If frequent premature ventricular contractions or serious ventricular arrhythmias are documented, we seriously consider antiarrhythmic therapy in an attempt to prevent ventricular tachyarrhythmias and sudden death.

Regional myocardial blood flow and cardiac mechanics in dog hearts with CO2 laser-induced intramyocardial revascularization.

Laser-induced intramyocardial revascularization (LIR) has been used to promote direct communications between blood within the ventricular cavity and that of the existing myocardial vasculature in an attempt to increase perfusion in patients with ischemic heart disease. This study was conducted to measure the effects of LIR channels on regional myocardial flood flow (microspheres), cardiac mechanics (sonomicrometers), and myocardial tissue pressures in 18 dogs. Under baseline hemodynamic conditions (mean HR = 165.2 +/- 11.4 bpm, LVP = 123.6 +/- 22.9/4.0 +/- 1.8 mm Hg, AoP = 112.8 +/- 27.1/77.0 +/- 22.5 mm Hg), myocardial blood flow in laser-treated tissue (mean = 1.11 +/- .10 cc/min/gm before laser; .71 +/- .19 cc/min/gm after laser) was reduced as compared to blood flow in control tissue (mean = 1.12 +/- .15 cc/min/gm before laser; 1.25 +/- .22 cc/min/gm after laser). Regional myocardial systolic shortening (11.32% +/- 3.82% before laser; 7.49% +/- 2.86% after laser) was decreased by 33%. During simultaneous reversible ligation of the LAD and LCCA for 2 min, when intramyocardial channels represented the only tissue access for the injected microspheres, blood flow in laser-treated tissue was not increased above that of the control non-lasered tissue. However, regional blood flow was greater in laser-treated ischemic tissue (mean = .61 +/- .12 cc/min/gm) than in untreated ischemic areas (mean = .04 +/- .03 cc/min/gm) when left ventricular pressure (LVP) was acutely elevated (mean SLVP = 207.0 +/- 16.1 mm Hg). Using these measurements, a model is proposed to predict regional systolic pressure gradients between the left ventricular cavity and coronary intramyocardial vasculature required to permit restoration of blood flow to ischemic myocardium. We conclude that improved perfusion via laser-induced intramyocardial channels does not occur in otherwise normal myocardium exposed to acute coronary ligation and only small improvements in perfusion are noted when LVP is significantly elevated. Consideration of further clinical application of this approach is seriously cautioned awaiting additional experimental studies.

Exercise testing in children before and after surgical treatment of aortic stenosis.

Twenty-three children with valvar or discrete subvalvar aortic stenosis underwent a controlled, progressive bicycle exercise test within 6 months before and 3-30 months after surgery for left ventricular outflow tract obstruction. The patients were divided into three groups according to the preoperative resting gradient of left ventricular to aortic peak systolic pressure: 30-69 mm Hg (group A), 70-99 mm Hg (group B), and greater than or equal to 100 mm Hg (group C). Preoperatively, 19 of 23 patients (83%) developed significant ST depression (greater than or equal to 1.0 mm) during exercise, whereas only seven (30%) had abnormal ST depression at rest. Postoperatively, mean exercise-induced ST depression regressed to less than 1 mm in all three groups. In the total population the frequency of ST depression greater than 1 mm was significantly reduced after surgical treatment and mean total work and peak exercise systolic blood pressure were significantly increased within 12 months after surgery. Total work increased significantly in group B within 12 months and in group C within 13-24 months after surgery, but remained unchanged on group A. Peak exercise heart rates were similar before and after surgery in each group. Peak exercise systolic pressures increased after surgery in all three groups, but the mean differences were statistically significant only in group C patients tested 13-24 months after surgery. The results of this study show that exercise testing is useful for quantifying the severity of aortic stenosis and documenting the clinical improvement (or lack thereof) after surgical treatment, and that properly supervised exercise testing can be performed at minimal risk to children with significant aortic stenosis.