Outcomes of elderly patients with nondisplaced or minimally displaced femoral neck fractures treated with internal fixation: A systematic review and meta-analysis.

BACKGROUND: Internal fixation remains the treatment of choice for non-displaced femoral neck fractures in elderly patients. Improved outcomes with arthroplasty following displaced femoral neck fractures may indicate that outcomes of non-displaced patterns should be reexamined. The aim of our study was to conduct a systematic review of the orthopaedic literature to determine the outcomes of internal fixation for the treatment of non-displaced and minimally displaced femoral neck fractures in elderly patients. METHODS: Relevant articles were identified using PubMed, Embase, and CENTRAL databases. Manuscripts were included if they contained (1) patients 60 years or older with (2) nondisplaced or minimally displaced (Garden I or II) femoral neck fractures (3) treated with internal fixation (4) separately reported outcomes in this patient population. The primary outcome was reoperation. Secondary outcomes included mortality, patient-reported outcomes, length of hospitalization, infection, and transfusions. Fixed and random effects modeling was used to determine pooled estimates of the outcomes. RESULTS: Twenty-seven studies were identified with a total of 21,155 patients, all of which were treated with internal fixation. The pooled risk of reoperation was 14.1% (95% CI: 10.6-18.2). The risk of one-year mortality was 14.6% (95% CI: 11.5-18.2) based on the reporting in 15 studies. CONCLUSIONS: The risk of reoperation and mortality following the treatment of nondisplaced femoral neck fractures in the elderly with internal fixation exceeds 14%. This complication profile may be unacceptably high. Arthroplasty may offer improved short-term functional outcomes and a reduced risk of reoperation. However, there is currently little evidence to consider this treatment to be an alternative to internal fixation.

CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease.

Single-nucleotide polymorphisms (SNPs) in the CYP2C gene cluster have been extensively investigated as predisposing factors for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB). However, results have been inconclusive owing to different study designs, limited genotyping strategies, and small sample sizes. We investigated whether eight functional SNPs in the CYP2C family of genes--CYP2C8*3 (rs11572080 and rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17--are associated with PUD in 1,239 Caucasian patients. Logistic regression analysis showed that only CYP2C19*17 was associated with PUD (odds ratio additive model: 1.47 (95% confidence interval (CI) 1.12 to 1.92); P = 0.005; R(2) 16%), but not UGIB, independent of NSAID use or Helicobacter pylori infection. PUD distribution varied (P = 0.024) according to CYP2C19*17 genotype: *1/*1, 490 (64.3%); *1/*17, 304 (71.7%); and *17/*17, 31 (73.8%). CYP2C19*17, a gain-of-function polymorphism, is associated with PUD irrespective of etiology.

Promoting physical activity and a healthful diet among children: results of a school-based intervention study.

BACKGROUND: National health objectives call for improved diet and more regular physical activity among children. We tested the effects of a school-based program to improve students' diet and physical activity behavior at school. METHODS: Two of the four elementary schools in one Texas school district were assigned to intervention and two to control conditions. The three intervention components were classroom health education, vigorous physical education, and lower fat, lower sodium school lunches. Nutrients from school lunches and the total day and the amount of physical activity students obtained during physical education were assessed as outcome. RESULTS: Analysis of school lunches showed declines from base line to posttest in the two intervention schools of 15.5% and 10.4% for total fat, 31.7% and 18.8% for saturated fat, and 40.2% and 53.6% for sodium; posttest values were lower in the intervention schools. Observation of physical activity during physical education classes indicated an increase in the intervention schools from baseline to posttest in the percent of time children engaged in moderate-to-vigorous physical activity from less than 10% of class time at baseline to about 40% of class time at posttest; posttest values were higher in the intervention schools than in the control schools. CONCLUSIONS: This efficacy study demonstrates the feasibility of substantially modifying school lunches and school physical education to improve children's diet and physical activity behavior at school.

Children's frequency of participation in moderate to vigorous physical activities.

Third and fourth grade boys (n = 422) and girls (n = 390) in four Texas elementary schools reported their participation in moderate to vigorous physical activities (MVPAs) over a 3-day period. Students were surveyed during class on successive days. On a subsample (n = 44), the agreement between reported and observed physical activities during physical education or recess was 86.3%. Running, walking fast, games and sports, and bicycling accounted for 70% of Total MVPAs. Of Total MVPAs reported, 47.0% for boys and 44.6% for girls were 10 min or longer in duration (LMVPA). The average number of LMVPAs per day was 1.7 for both boys and girls. Students reported significantly more occurrences of LMVPAs out of school than during school. Significant interaction between grade and gender indicated that third grade boys reported more Total MVPAs and LMVPAs than third grade girls, but fourth grade boys reported fewer Total MVPAs and LMVPAs than fourth grade girls reported fewer Total MVPAs and LMVPAs than fourth grade girls. During the 3-day reporting period, 12.3% of boys and 13.3% of girls reported no LMVPAs, and 35.6% of boys and girls reported fewer than one LMVPAs per day. While the majority of children reported obtaining at least some activity daily, a substantial proportion of children in this sample reported fewer than one LMVPA daily, indicating that many children may not be obtaining adequate amounts of physical activity.

Children's frequency of consumption of foods high in fat and sodium.

We administered a food frequency instrument to third-fifth grade students (n = 943) in four Texas schools. Comparison of foods reported on the food frequency questionnaire and on 24-hour dietary recalls (n = 7) produced a percent agreement of 83.3. The most frequent 25 foods accounted for 64.0% of food choices across all meals, 93.5% of breakfast choices, 76.4% of lunch choices, 70.5% of supper choices, and 76.0% of snack choices. Breads, milk, hamburger or steak, soda pop, tomato sauce or tomatoes, and cheese were the most frequently consumed foods. Fruits and juices accounted for 6.1% of total selections for boys and 6.6% for girls, while vegetables accounted for 15.7% of total selections for boys and 16.2% for girls. Fruit was more likely to be consumed for snacks than for meals, and vegetables were consumed in about the same frequency at lunch and supper and for snacks. We analyzed the total fat, saturated fat, and sodium content of the most frequently consumed foods. Seventeen of the top 25 foods for the total day and 13-16 for each meal or snack exceeded by at least 50% the recommended levels for fat, saturated fat, or sodium. The pattern of consumption was one of frequent consumption of a relatively small number of foods, many of which are high in fat or sodium.

Validity of the observation of children's physical activity.

An observational method for quantifying intensity of activity was validated against min-by-min heart rates during physical education periods. The mean heart rate values increased as the activity points increased. Moderate average correlations were obtained between the min-by-min activity points and heart rates. A time series regression analysis accounted for 72% of the variance in heart rate values with a model combining heart rate in the previous min and activity points. Further work on estimates of average metabolic units for activity categories will enable future investigators to obtain more precise estimates of energy expenditure from this observation system.

School promotion of healthful diet and physical activity: impact on learning outcomes and self-reported behavior.

The Go For Health Program included classroom health education and environmental changes in school lunch and physical education to foster healthful diet and exercise among elementary school children. Interventions were based on social learning theory and implementation was based on an organizational change strategy for school innovations. Two schools were assigned to intervention and two to control conditions. Cognitive measures (behavioral capability, self-efficacy, behavioral expectations) and self-reported diet and exercise behavior were assessed at baseline and following intervention. Data were analyzed by ANOVA using the student and then the school as the unit of analysis. Statistically significant changes were observed for diet behavioral capability, self-efficacy, and behavioral expectations, use of salt, and exercise behavioral capability (fourth grade), self-efficacy (fourth grade) and frequency of participation in aerobic activity. The results provide evidence for program impact on learning outcomes and student behavior.

Implementing organizational changes to promote healthful diet and physical activity at school.

Diet and physical activity patterns appear to be learned at early ages, suggesting the need for school-based intervention. The potential of schools to improve children's diet and physical activity has been offset by countervailing school environments. In the first year of the "Go For Health" health promotion project, organizational change innovations were implemented to facilitate changes in school lunch, physical education, and classroom health education in support of healthful student diet and physical activity. At first follow-up after one year of intervention, the amount of sodium in selected foods served in school lunch was reduced from baseline (1985) to year one (1986) in the experimental schools by 29 and 33%, respectively, and fat was reduced by 28 and 42%, respectively. At first follow-up, students in the experimental schools participated in fitness activities 44.1 and 38.0% of the time, compared with 19.5 and 22.7% in the control schools.

School promotion of healthful diet and exercise behavior: an integration of organizational change and social learning theory interventions.

In the Go For Health project, interventions based on organizational change and social learning theory facilitate changes in diet and exercise behavior by elementary school children. Baseline data documented the need for behavior change. Based on chemical analyses, average per meal amounts of total fat and sodium were higher than national recommendations: total fat was 29.3% higher than U.S. Dietary Goals; sodium was 107.4% greater than recommended levels. Observations of students in physical education class revealed children moved through space 50.1% of the time and moved continuously an average of 2.2 minutes per class period. These findings suggest the need for policy and practice changes in the school environment to enable children to engage in more healthful diet and exercise behavior.

Direct evidence for the interaction between papaverine and alpha 2-adrenergic receptors in canine platelets.

The effects of papaverine on specific [3H]-yohimbine binding to canine platelet alpha 2-adrenergic receptors and on the platelet aggregation were assessed and compared with those of verapamil. Both compounds concentration-dependently inhibited [3H]-yohimbine binding with KI values for respective compounds of 0.39 +/- 0.05 microM (n = 3) and 15 +/- 0.19 microM (n = 3). In the presence of either compound KD values in Scatchard analysis of the equilibrium ligand binding increased in concentration-dependent manner, whereas Bmax did not change, indicating competitive inhibition of the ligand binding by these compounds. (-)-Epinephrine (3 microM) potentiation of adenosine diphosphate (ADP, 0.1 microM) aggregation was inhibited by papaverine with IC50 of 11 +/- 3.6 microM (n = 4). In the same experiments verapamil inhibited the platelet aggregation with lower IC50 (3.1 +/- 0.87 microM, n = 4) in comparison with that for papaverine. These results suggest that papaverine, like verapamil, inhibits physiological response of canine platelets through alpha-adrenergic receptor stimulation by direct interaction with the receptors.

Papaverine inhibits binding of [3H]-prazosin and [3H]-yohimbine to rat renal cortical membranes.

We examined the effects of papaverine on specific [3H]-prazosin and [3H]-yohimbine bindings to rat renal cortical membranes and compared these effects with those of verapamil. Papaverine inhibited both ligand bindings with KI values of 4.2 +/- 1.7 microM and 48.4 +/- 8.7 microM (N = 5) in the inhibition of [3H]-prazosin and [3H]-yohimbine bindings, respectively. In contrast with verapamil, which competitively inhibited both ligand bindings, papaverine inhibited them in a different manner. Although the affinities of these ligand binding sites for papaverine are low, alpha-receptor blockade is a possible mechanism of action of this compound.

Alpha 2-adrenergic receptors on canine platelet membranes characterized by [3H]-yohimbine binding.

Alpha 2-adrenoceptors on canine platelet membranes were characterized by [3H]-yohimbine binding. Binding of [3H]-yohimbine to the membranes was rapidly saturated, stable and reversible with high affinity. Dissociation constant (KD) calculated from Scatchard analysis of the equilibrium experiments was 1.89 +/- 0.20 nM which was in good agreement with KD (1.97 +/- 0.60 nM) obtained in the kinetic experiments. Maximal binding sites of the ligand (Bmax) was 249 +/- 20 fmoles/mg protein. Adrenergic antagonists inhibited the ligand binding in following rank order of potency; yohimbine greater than phentolamine greater than phenoxybenzamine greater than corynanthine greater than prazosin. This order was in good correlation with that for these drugs in the inhibition of platelet aggregation. Hill coefficients for the displacement curves of the ligand binding by adrenergic agonists were less than 1.0 which were converted into near unity in the presence of 5'-guanylyl-imidodiphosphate (100 microM). These results demonstrate that canine platelet membranes have alpha 2-adrenoceptors and suggest that the binding of these receptors to adrenergic agonists is regulated by guanine nucleotides.

Effect of propranolol, alprenolol, pindolol, and bopindolol on beta 2-adrenoceptor density in human lymphocytes.

Abrupt withdrawal of beta-adrenoceptor antagonists may lead to "rebound effects." To investigate the position of the new nonselective beta-adrenoceptor antagonist bopindolol [with moderate intrinsic sympathomimetic activity (ISA)], this drug was compared with propranolol (no ISA), alprenolol (weak ISA), and pindolol (marked ISA). The effects on lymphocyte beta 2-adrenoceptor density--assessed by (+/-)-[125I]iodocyanopindolol (ICYP) binding--were investigated in healthy volunteers aged 23-35 years. None of the test drugs changed the affinity of ICYP for beta 2 adrenoceptors. Propranolol treatment (4 X 40 mg/day) increased the density of beta 2-adrenoceptors by 25% after 2 days; during treatment beta 2-adrenoceptor density remained elevated. After withdrawal of propranolol, beta 2-adrenoceptor density declined slowly, being still significantly increased after 3 days, although propranolol was not detectable in plasma after 24 h, though heart rate was significantly increased. Alprenolol treatment (4 X 100 mg/day) did not significantly affect beta 2-adrenoceptor density. Pindolol treatment (2 X 5 mg/day) caused a 50% decrease of beta 2-adrenoceptor density after 2 days, which remained reduced during treatment. After withdrawal, beta 2-adrenoceptor density was still significantly diminished after 4 days. During and after treatment heart rate was not affected. Bopindolol treatment (2 mg/day) caused a 40% decrease of beta 2-adrenoceptor density after 2 days, which remained reduced during treatment. After withdrawal, beta 2-adrenoceptor density was still significantly diminished after 4 days. During and after treatment heart rate was not affected. It is concluded that the ISA may play an important role in modulating beta 2-adrenoceptor density and hence tissue responsiveness to beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute regulation of lymphocyte beta 2-adrenoceptors is altered in patients with essential hypertension.

The effects of acute stimulation of the sympathetic activity by dynamic exercise on lymphocyte beta 2-adrenoceptor density [assessed by (-)-125iodocyanopindolol (ICYP) binding] and responsiveness [10 mumol/l isoprenaline-induced cyclic adenosine monophosphate (cAMP) increases] were studied in 10 normotensive (Pdiast < 90 mmHg) volunteers and in 10 patients with established essential hypertension (Pdiast > 95 mmHg). In normotensives, dynamic exercise on a bicycle (80% of maximum heart rate) for 15 min led to an increase in lymphocyte beta 2-adrenoceptor density from 1080 +/- 77 to 2033 +/- 152 ICYP binding sites/cell; concomitantly isoprenaline-induced increase in lymphocyte cAMP was enhanced. This effect appears to be mediated by beta 2-adrenoceptor stimulation, since the exercise-induced increase in beta 2-adrenoceptor density was markedly attenuated by pretreatment of the volunteers with propranolol (5 mg intravenously 45 min before exercise), but not by pretreatment with the beta 1-selective antagonist bisoprolol (2.5 mg intravenously 30 min before exercise). In patients with essential hypertension, lymphocyte beta 2-adrenoceptor density (1512 +/- 101 ICYP binding sites/cell) was significantly higher than in controls (P < 0.05); the same held true for isoprenaline-induced cAMP increases. In these patients, however, dynamic exercise caused only a slight increase in lymphocyte beta 2-adrenoceptor density (to 1859 +/- 154 ICYP binding sites/cell) and in isoprenaline-induced cAMP increases. From these results it is concluded that in essential hypertension acute regulation of the beta-adrenoceptor/adenylate cyclase system is impaired.

Terbutaline-induced desensitization of human lymphocyte beta 2-adrenoceptors. Accelerated restoration of beta-adrenoceptor responsiveness by prednisone and ketotifen.

We investigated, in 36 healthy volunteers, the effects of prednisone and ketotifen on recovery of lymphocyte beta 2-adrenoceptor density (determined by (-)-125iodocyanopindolol binding) and responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 microM (-)-isoprenaline) after desensitization by the beta 2-agonist terbutaline. Terbutaline (3 X 5 mg/d) decreased lymphocyte beta 2-adrenoceptor density by approximately 40-50%; concomitantly, lymphocyte cAMP responses to 10 microM (-)-isoprenaline were significantly reduced. After withdrawal of terbutaline beta 2-adrenoceptor, density and responsiveness gradually increased, reaching predrug levels after 4 d. Prednisone (1 X 100 mg orally) accelerated beta 2-adrenoceptor recovery; only 8-10 h after administration of the steroid beta 2-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached values not significantly different from pretreatment levels. Similar effects were obtained with ketotifen (2 mg; thereafter 2 X 1 mg/d for 4 d): 24 h after application of the drug beta 2-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached pretreatment levels. Furthermore, ketotifen simultaneously applied with terbutaline completely prevented terbutaline-induced decrease in lymphocyte beta 2-adrenoceptor density and responsiveness. Prednisone (1 X 100 mg orally) or ketotifen (2 mg; thereafter 2 X 1 mg/d for 2 d) had no significant influence on lymphocyte beta 2-adrenoceptor density in healthy volunteers not pretreated with terbutaline, but shifted the ratio high-to-low affinity state of the lymphocyte beta 2-adrenoceptor toward high affinity state. We conclude that glucocorticoids as well as ketotifen can accelerate recovery of density and responsiveness of lymphocyte beta 2-adrenoceptors desensitized by long-term treatment with beta 2-agonists. Such an effect may have clinical implications for preventing tachyphylaxis of asthmatic patients against therapy with beta 2-agonists.

Different mechanisms underlying reduced beta 2-adrenoceptor responsiveness in lymphocytes from neonates and old subjects.

To investigate the mechanism underlying age-dependent changes in beta-adrenoceptor function we have determined beta 2-adrenoceptor density (by (+/-)-125iodocyanopindolol (ICYP) binding) and beta 2-responsiveness (cyclic AMP responses to isoprenaline stimulation) in lymphocytes derived from 20 neonates, 54 young adults (19-30 years) and 15 old subjects (60-86 years). In young adults the mean number of lymphocyte beta 2-adrenoceptors amounted to 862 +/- 36 (range 500-1560) ICYP binding sites/cell (N = 54); it was slightly higher in old subjects with 1230 +/- 94 (698-1980) ICYP binding sites/cell (N = 15). In contrast, lymphocytes derived from neonatal blood had a significantly lower mean beta 2-adrenoceptor number (385 +/- 35 (130-608) ICYP binding sites/cell, N = 20, P less than 0.01). (-)-Isoprenaline (0.01-100 microM)-induced increases in lymphocyte cyclic AMP content were significantly lower in neonates and old subjects than in young adults. While for neonates and young adults significant positive correlations between beta 2-adrenoceptor density and 10 microM (-)-isoprenaline-induced cyclic AMP increases exist, in old subjects cyclic AMP increases were much lower than could be expected from the beta 2-adrenoceptor number. It is concluded that the mechanism underlying reduced beta 2-adrenoceptor responsiveness in neonates and old subjects is different: while in neonates it seems to be due to the reduced beta-adrenoceptor number, in old subjects it is caused by a post-receptor defect--presumably by a decreased activity of the adenylate cyclase.

Effects of beta-adrenoceptor antagonist administration on beta 2-adrenoceptor density in human lymphocytes. The role of the "intrinsic sympathomimetic activity".

Abrupt withdrawal of beta-adrenoceptor antagonists may lead to "rebound-effects". To study the mechanism underlying this phenomenon, the effects of the nonselective beta-adrenoceptor antagonists propranolol [no intrinsic sympathomimetic activity (ISA)], alprenolol (weak ISA) and mepindolol (strong ISA) on lymphocyte beta 2-adrenoceptor density--assessed by (+/-)-[125I]-iodocyanopindolol (ICYP) binding--and plasma renin activity (PRA) were investigated in male healthy volunteers aged 23-35 years. Propranolol treatment (4 X 40 mg/day) increased the density of beta 2-adrenoceptors by 25% after 2 days; concomitantly PRA and heart rate were reduced. During treatment beta 2-adrenoceptor density remained elevated. After withdrawal of propranolol PRA reached pre-drug levels rapidly, while heart rate was significantly enhanced. Beta 2-Adrenoceptor density, however, declined slowly being still significantly increased after 3 days, although propranolol was not detectable in plasma after 24 h. The affinity of ICYP to beta 2-adrenoceptors was not changed during or after treatment. Mepindolol treatment (2 X 5 mg/day) caused a 30% decrease of beta 2-adrenoceptor density and PRA after 2 days; both parameters remained reduced during treatment. After withdrawal, PRA reached rapidly pre-drug levels, whereas beta 2-adrenoceptor density was still after 4 days significantly diminished. The KD-values for ICYP, however, were not changed. During and after treatment heart rate was not affected. Alprenolol treatment (4 X 100 mg/day) led to a rapid fall in PRA, but did not significantly affect beta 2-adrenoceptor density. It is concluded, that the ISA may play an important role in modulating beta 2-adrenoceptor density and hence tissue responsiveness to beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Properties of alpha- and beta-adrenoceptors in circulating blood cells of patients with essential hypertension.

The properties of platelet alpha 2-adrenoceptors and of lymphocyte beta 2-adrenoceptors were determined in 40 male patients with established essential hypertension and compared with those in 40 male normotensives. The densities of platelet alpha 2-adrenoceptors (assessed by 3H-yohimbine binding) and of lymphocyte beta 2-adrenoceptors [determined by (+/-)-125iodocyanopindolol binding] were in patients with essential hypertension significantly higher than in controls; there were significant positive correlations between the mean arterial blood pressure of the subjects and alpha 2- and beta 2-adrenoceptor density, respectively. Concomitantly with receptor densities, functional responses to adrenergic stimulation were exaggerated in essential hypertension: in platelets, the aggregatory response to (-)-adrenaline (via alpha 2-adrenoceptor stimulation) was enhanced; in lymphocytes, the cyclic AMP response to (-)-isoprenaline (via beta 2-adrenoceptor stimulation) was elevated. It is concluded that the increased adrenoceptor density and responsiveness in circulating blood cells of patients with essential hypertension may reflect increased sympathetic activity, which might contribute to the elevation of blood pressure.