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Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models.

Repressor element-1 silencing transcription factor (REST) is a candidate modulator of gene expression during status epilepticus in the rodent. In such models, full-length REST and the truncated REST4 variant are induced and can potentially direct differential gene expression patterns. We have addressed the regulation of these REST variants in rodent hippocampal seizure models and correlated this with expression of the proconvulsant, substance P encoding, PPT-A gene. REST and REST4 were differentially regulated following kainic acid stimulus both in in vitro and in vivo models. REST4 was more tightly regulated than REST in both models and its transient expression correlated with that of the differential regulation of PPT-A. Consistent with this, overexpression of a truncated REST protein (HZ4, lacking the C-terminal repression domain) increased expression of the endogenous PPT-A gene. Similarly the proximal PPT-A promoter reporter gene construct was differentially regulated by the distinct REST isoforms in hippocampal cells with HZ4 being the major inducer of increased reporter expression. Furthermore, REST and REST4 proteins were differentially expressed and compartmentalized within rat hippocampal cells in vitro following noxious stimuli. This differential localization of the REST isoforms was confirmed in the CA1 region following perforant path and kainic acid induction of status epilepticus in vivo. We propose that the interplay between REST and REST4 alter the expression of proconvulsant genes, as exemplified by the PPT-A gene, and may therefore regulate the progression of epileptogenesis.

Animals↗

Effect of coronary artery bypass surgery on myocardial perfusion and ejection fraction response to inotropic stimulation in patients without improvement in resting ejection fraction.

The aim of this study was to assess the effect of coronary artery bypass grafting (CABG) on myocardial perfusion and left ventricular (LV) contractile reserve in patients with reduced ejection fraction (EF). We studied 57 patients (age 59 +/- 8 years, 46 men and 11 women) with EF < or = 40% referred for CABG with dobutamine (up to 40 microg/kg/min) stress-reinjection thallium-201 single-photon emission computed tomography, and radionuclide ventriculography at rest and at low-dose dobutamine before and 3 months after CABG. An increase in resting EF > or = 5% occurred in 12 patients (group A) after CABG (EF 34% before and 46% after CABG), whereas no increase occurred in the remaining 45 patients (group B) (EF 34% before and 32% after CABG). A significant increase in EF from rest to low-dose dobutamine radionuclide ventriculography occurred before and after CABG. The magnitude of increase was more significant after than before CABG in group A (12% vs 7%) as well as in group B (13% vs 7%, both p <0.001). Patients in both groups had a significant reduction in stress, rest, and ischemic perfusion scores after CABG. However, the percentage of reduction in resting perfusion defect score was more significant in group A than in group B (60% vs 30%, respectively, p <0.01). It is concluded that CABG induces a significant improvement in resting myocardial perfusion and EF response to inotropic stimulation, even in the absence of improved EF at rest. Patients without improvement in resting EF after CABG have mild improvement in resting myocardial perfusion that may be sufficient to increase EF after CABG during inotropic stimulation, but not at rest. We describe the myocardium with these characteristics as "the reactive myocardium."

Cardiotonic Agents↗

Left and right ventricular function at rest and during bicycle exercise in the supine and sitting positions in normal subjects and patients with coronary artery disease. Assessment by radionuclide ventriculography.

To assess the hemodynamic influence of posture during radionuclide cardiac studies, rest and exercise electrocardiographically gated blood pool cardiac scintigraphy was performed in the supine and sitting positions in 22 normal subjects and in 20 patients with coronary artery disease (CAD). In normal subjects, left ventricular ejection fraction was higher in the sitting position both at rest (67 +/- 6% versus 64 +/- 5%, p less than 0.01) and during exercise (79 +/- 9% versus 76 +/- 6%, p less than 0.05). Left ventricular end-diastolic volume in the sitting position was smaller at rest (by 19 +/- 26%, p less than 0.001), but this variable was similar in both positions during exercise (p greater than 0.05). Left ventricular end-systolic volume was smaller in the sitting position both at rest, by 26 +/- 31 percent, and during exercise, by 14 +/- 20% (p less than 0.001). Left ventricular end-diastolic volume increased from rest to exercise, in the sitting position by 31 +/- 23% (p less than 0.001) and in the supine position by 6 +/- 22% (p greater than 0.05). In patients with CAD, similar left ventricular ejection fractions in both postures were found at rest and during exercise. Left ventricular end-diastolic volume in the sitting posture was smaller at rest by 16 +/- 22% (p less than 0.01) and during exercise by 8 +/- 18% (p less than 0.05). Sitting left ventricular end-systolic volume was smaller by 18 +/- 20% (p less than 0.001) at rest and by 14 +/- 21% (p less than 0.01) during exercise. Left ventricular end-diastolic volume increased from rest to exercise, in the sitting position by 45 +/- 36% (p less than 0.001) and in the supine position by 32 +/- 51% (p less than 0.01). Despite significant hemodynamic differences, the value of rest-exercise radionuclide cardiac studies to detect CAD was similar in the 2 positions.

Adult↗

Mandibular rest position and electrical activity of the masticatory muscles.

STATEMENT OF PROBLEM: The determination of a correct vertical dimension of occlusion is a critical procedure in clinical dentistry. PURPOSE: The objectives of this study were to analyze the relation between mandibular rest position and electrical activity of masticatory muscles and to compare clinical and electromyographic rest position in subjects with different vertical facial morphologic features. MATERIAL AND METHODS: Clinical rest position and electromyographic rest position were investigated in 40 subjects. Electromyographic rest position ranged from 0.4 to 12.7 mm (average 7.7 +/- 2.7 mm). Clinical rest position ranged from 0.1 to 4.4 mm (average 1.4 +/- 1.1 mm). The average difference between electromyographic rest position and clinical rest position was 6.3 +/- 2.5 mm (range 0.3 to 10.3 mm). Sixteen subjects were selected according to the Frankfort mandibular plane angle and separated in two groups having a mandibular plane angle > or = 28 degrees. RESULTS: Rest position was significantly greater (p < 0.05) in the low-angle group (2 +/- 1.3 mm) than in the high angle group (0.8 +/- 0.8 mm). Electromyographic rest position did not differ between subjects with different facial morphologic features (8.1 +/- 1.7 mm low-angle group; 7.6 +/- 4.1 mm high angle group). By varying the vertical dimension millimeter by millimeter, masseter and anterior temporal electromyographic activity demonstrated a considerable decrease over an interocclusal distance of 3 to 4 mm. Further mandibular opening up to 18 mm corresponded to small changes in postural activity. CONCLUSION: This study suggests that a jaw posture with a few millimeters of interocclusal distance involves a great reduction of masticatory muscle activity.

Adult↗

Relationships between children's cardiovascular stress responses and resting cardiovascular functioning 1 year later.

Resting cardiovascular parameters were predicted from anthropometric data, resting baseline cardiovascular data, and cardiovascular responses to three laboratory stressors completed 1 year earlier. Subjects were 106 male and female children (72 Whites, 34 Blacks) aged 6-7 years at the initial evaluation. During initial testing, blood pressure, heart rate, cardiac output, and total peripheral resistance were assessed at rest and also during a forehead cold pressor task, postural change, and treadmill exercise. The same cardiovascular parameters were then assessed at rest 1 year later. After controlling for significant anthropometric measures and the pertinent previous year's resting data, systolic and diastolic responses to the cold pressor were predictive of respective follow-up resting levels. Postural change heart rate responses were predictive of follow-up resting heart rate after controlling for initial resting levels. Exercise cardiac index reactivity predicted follow-up cardiac index after controlling for earlier resting levels and adiposity. Follow-up total peripheral resistance index was predicted by earlier resting levels.

Blood Pressure↗

The relevance of resting tension to responsiveness and inherent tone of human bronchial smooth muscle.

1. In the present study the effects of resting tension on isometric responses of human airway smooth muscle to contractile and relaxant stimuli were investigated. Also, its effects on inherent smooth muscle tone were examined, in an effort to determine a pre-defined resting tension which can be considered optimal for in vitro studies. 2. Bronchial ring preparations (2-4 mm internal diameter) were suspended in tissue baths at a range of levels of resting tension (200-1600 mg). The responses to electrical field stimulation (EFS, 30 V, 0.2 ms, 8-30 Hz), carbachol (3 microM), isoprenaline (1 microM) and the 5-lipoxygenase inhibitor, zileuton (10 microM) were investigated along with the ability of the preparations to recover stable resting tension after 60 min of washing post challenge. 3. EFS induced monophasic contractions at low stimulation frequency (8 Hz). However, with increasing frequency and tension (15 and 30 Hz; > 400 mg) contractile responses were accompanied by a relaxant component. The magnitude of contractile responses increased with increasing resting tension to a plateau at between 500 and 700 mg. Relaxant responses when present, increased in magnitude with increasing resting tension. 4. The level of resting tension did not significantly alter responses to carbachol, but tissues at tensions > or = 1000 mg showed poor tension recovery after washing. Isoprenaline-induced relaxations increased with increasing resting tension (P<0.05) and tension recovery after washing was complete. The 5-lipoxygenase sensitive portion of the tension (33+/-4%) was not altered by the level of resting tension. 5 These results suggest that in human bronchial ring preparations of 2-4 mm internal diameter, resting tensions within the range 400-1000 mg could be considered optimal for isometric tension recordings of protocols involving both contraction and relaxation procedures.

Adult↗

Habitual meal frequency in relation to resting and activity-induced energy expenditure in human subjects: the role of fat-free mass.

Habitual meal frequency was assessed as a possible function of components of energy expenditure (EE) in human subjects. Fifty-six subjects participated (four categories differing in body composition): ten older women (fat-free mass (FFM) 42.0 (sd 6.3) kg, aged 59 (sd 2) years, BMI 27.5 (sd 6.9) kg/m(2)), fifteen younger women (FFM 45.5 (sd 5.2) kg, aged 34 (sd 10) years, BMI 21.9 (sd 2.3) kg/m(2)), twelve older men (FFM 56.8 (sd 5.9) kg, aged 62 (sd 4) years, BMI 25.7 (sd 3.3) kg/m(2)) and nineteen younger men (FFM 63.9 (sd 7.5) kg, aged 23.1 (sd 3.9) years, BMI 22.9 (sd 1.8) kg/m(2)). Measurements consisted of habitual meal frequency by validated food-intake diaries, physical activity by tri-axial accelerometers and resting EE by a ventilated hood system. Habitual meal frequency was expressed as a function of resting EE (including resting EE as a function of FFM), and of activity-induced EE, using regression analysis. FFM differed according to gender and age categories (P<0.01). Physical activity level was higher in the younger men than in the other categories (P<0.05). No relationship of meal frequency with the variables assessed was observed in subjects with a low FFM (the women). In the subjects with a medium FFM (the older men), meal frequency was positively related to resting EE (r(2) 0.4, P<0.05), but not to the residuals of resting EE as a function of FFM, and inversely related to activity-induced EE (r(2) 0.3, P<0.05). Resting EE explained 40 % of the variation in meal frequency; adding activity-induced EE increased this to 60 %. In the subjects with a high FFM (the younger men), meal frequency was inversely related to resting EE (r(2) 0.8, P<0.0001) and to the residuals of resting EE as a function of FFM (P=0.03), and positively related to activity-induced EE (r(2) 0.6, P<0.0001). Resting EE explained 85 % of the variation in meal frequency; adding activity-induced EE increased this to 89 %. Habitual meal frequency was a function of components of EE, namely resting EE and activity-induced EE, only in subjects with a medium to high FFM (men). FFM-related differences in these relationships suggest a role of physical activity.

Adult↗

Head-to-head comparison of 201Tl rest-redistribution scintigraphy and stress-immediate reinjection scintigraphy in the detection of myocardial viability.

Reinjection imaging with thallium-201 (201Tl) provides a reliable method of identifying viable myocardium. Reinjection of 201Tl immediately after completing the stress images followed by imaging 1 h after reinjection shortens the examination time to a maximum of 2.5 h and provides an alternative imaging approach in patients with coronary artery disease. In this study, we investigated whether immediate 201Tl reinjection imaging provides adequate information on myocardial viability compared with separate-day 201Tl rest or rest-redistribution imaging. In 23 patients with anterior or anteroseptal wall infarction first documented more than 3 months previously, we performed 201Tl stress-immediate reinjection, separate-day 201Tl rest imaging and rest-stress radionuclide angiography. In 13 patients, 201Tl rest scintigraphy was followed by redistribution imaging 3 h later. On the three-view planar 201Tl images, eight myocardial segments were analysed visually and quantitatively. Stress 201Tl images were compared with 201Tl reinjection images, 201Tl rest images and 201Tl 3-h redistribution images after rest injection. When comparing the stress images both with the immediate reinjection images and the rest images, concordant scintigraphic classification was found in 181 of 184 myocardial segments (kappa = 0.97). Comparing the stress images both with the immediate reinjection images and with the 3-h redistribution images following 201Tl injection at rest, concordant scintigraphic classification was found in 102 of 104 myocardial segments (kappa = 0.97). In 16 of 23 (70%) patients, 201Tl stress-immediate reinjection scintigraphy and radionuclide angiography provided concordant information on myocardial viability. In 6 (26%) patients, we observed a function-perfusion mismatch (i.e. 201Tl uptake in dyskinetic/adyskinetic regions) indicative of jeopardized but viable myocardium, demonstrating the additional value of 201Tl as a marker of viability. We conclude that stress-immediate 201Tl reinjection images provide information on myocardial viability and ischaemia in patients with previous myocardial infarction in addition to that obtained regarding wall motion abnormalities as assessed by rest-stress radionuclide angiography.

Adult↗

Expression of the repressor element-1 silencing transcription factor (REST) is influenced by insulin-like growth factor-I in differentiating human neuroblastoma cells.

The repressor element-1 (RE-1) silencing transcription factor (REST) interacts with an RE-1 cis element and represses the transcription of neuron-specific genes in neuronal progenitors but is down-regulated in post-mitotic neurons. We report that REST expression is modified, in a time-dependent manner, in SH-SY5Y neuroblastoma cells exposed to insulin-like growth factor I (IGF-I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF-I for 2 days and then declines in 5-day-treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF-I, we employed an antisense oligonucleotide (AS-ODN) complementary to REST mRNA. In AS-ODN-treated cells, the effects elicited by IGF-I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and betaIII-tubulin gene promoters contain an RE-1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF-I for 5 days and further elevated by AS-ODN treatment. A parallel increase of growth cone-associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF-I and could contribute to down-regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.

Antibodies↗

Effects of anions and cations on the resting membrane potential of internally perfused barnacle muscle fibres.

1. Single barnacle muscle fibres from Megabalanus psittacus (Darwin) were internally perfused with a number of K salt solutions (200 mM) which were made isotonic to the barnacle saline with sucrose.2. 200 mM-K acetate solution, in general, was found to be more effective than other solutions of K salts in generating and maintaining stable resting membrane potential of -56.0 +/- 0.7 mV (all potentials are referred to the external solutions as ground). The various K salts, on the basis of the magnitude of the resting potential they generated in the muscle fibres, followed the sequence, acetate > isethionate > aspartate > glutamate > fluoride > monohydrogen phosphate > succinate > citrate > sulphate > oxalate > iodobenzoate > ferrocyanide > chlorate > nitrate > chloride > thiocyanate > iodide > bromide > cyanide.3. The resting potential in muscle fibres perfused with solutions of acetate, aspartate and glutamate increased linearly with the logarithm of the K concentration (slope = 30.4 mV for K acetate and 27.4 for K aspartate and glutamate) when the ionic strength of the solutions was progressively increased from 50 to 650 mM. On the other hand, similar increase of ionic strength beyond 200 mM of solutions of K isethionate, fluoride, monohydrogen phosphate, succinate and citrate depolarized the muscle fibres.4. Perfusion of acetate solutions of other alkali metal ions gave low values for the resting potential and followed the sequence K > Na > Rb > Li > Cs. Also NH(4) and Tris ions gave low values for the resting potential which underwent oscillations associated with the twitching of the fibre and occasionally became positive in value (action potential).5. Addition of tetraethyl ammonium chloride (TEA-Cl), 20-100 mM, to K acetate solutions (200 mM) depolarized the fibre membrane and the consequent reduction of resting potential varied linearly with the logarithm of TEA concentration.6. Replacement of chloride ion by acetate or isethionate in the external solution did not change significantly the resting potential although the values were consistently lower by about 2 mV.7. Complete elimination of K in the external solution and reduction of its ionic strength using sucrose depolarized the muscle fibres by about 27 mV when Na was changed from 475 to 1 mM. Under these conditions, external solutions completely in acetate form gave resting potentials which were more positive than those observed in completely chloride solutions by 6-8 mV.8. Replacement of Na by Li, Tris, choline, tetramethyl or tetraethyl ammonium ion in the external solution made the values of the resting potential more positive (depolarization). Similarly increasing the concentration of K (or Cs or Rb in place of K) by correspondingly decreasing the concentration of Na in the outside solution depolarized the fibres and the resting potential became zero at a concentration of 280 mM (or 308 or 1500 mM for Rb or Cs, respectively) on extrapolation.

Acetates↗

Endurance exercise training augments diastolic filling at rest and during exercise in healthy young and older men.

BACKGROUND: Diastolic filling at rest is altered markedly with advancing age. Whether exercise training can improve diastolic filling at rest or during exercise in either healthy older or healthy young men has not been determined. The purpose of this study was to determine if 6 months of aerobic exercise training improves diastolic filling. METHODS AND RESULTS: Radionuclide diastolic filling parameters were measured at rest and during exercise in 14 older (age, 60 to 82 years) and 17 young (age, 24 to 32 years) rigorously screened healthy males before exercise training and in 13 older and 11 young men after 6 months of endurance exercise training. Diastolic filling rates were expressed in two ways, as absolute milliliters of blood (mL.s-1.m-2) and normalized to the end-diastolic volume. At baseline, the peak early filling rates were lower in the older group compared with the young group as expressed in absolute milliliters of blood (older, 85 +/- 7 mL.s-1.m-2; young, 173 +/- 10 mL.s-1.m-2; P < or = .0001) and in end-diastolic volume per second (1.66 +/- 0.11 versus 2.55 +/- 0.08, P < .0001), whereas the peak atrial filling rates were greater in absolute milliliters of blood (85 +/- 5 versus 56 +/- 7 mL.s-1.m-2, P = .003) and in end-diastolic volume per second (1.70 +/- 0.12 versus 0.80 +/- 0.06, P < .0001). During exercise, at any given heart rate, the older group had a lower peak filling rate than the young group. Also, at peak exercise, the single peak filling rate was decreased in the older group in mL.s-1.m-2 (384 +/- 19 versus 565 +/- 36 mL.s-1.m-2, P = .0002) and in end-diastolic volume per second (6.01 +/- 0.25 versus 7.91 +/- 0.28 end-diastolic volume per second, P < .0001). Six months of intensive aerobic exercise training had similar effects in the old and young groups overall. Maximal oxygen consumption increased 19% (ANOVA training effect, P < or = .0001) and echocardiographic left ventricular mass increased 8% (ANOVA training effect, P = .002). Training increased the resting peak early filling rate in absolute milliliters of blood by +14% (ANOVA training effect, P = .02). During exercise, the peak early or single peak filling rate at any given heart rate was increased. At peak exercise, the single peak filling rate was increased by 14% in mL.s-1.m-2 (ANOVA training effect, P = .0004). The only age-related differential effect of training was on the peak atrial filling rate in end-diastolic volume per second, which decreased by 27% in the older group but was unchanged in the young (+5%) (ANOVA young versus older, P = .001). The independent predictors of a greater maximal oxygen consumption by multivariate analysis were a higher peak exercise heart rate, a greater resting peak early filling rate, the exercise trained state, and a younger age. CONCLUSIONS: Healthy older men have reduced early diastolic filling at rest and during exercise compared with young men. Endurance exercise training enhances early diastolic filling at rest and during exercise in both the old and the young. Training reduces the elevated resting atrial filling rate in the old, whereas the young were unchanged. The training-induced augmentation of early diastolic filling at rest and during exercise may be an important adaptation to allow an increase in stroke volume at rest and an increase in stroke volume, cardiac output, and maximal oxygen consumption during exercise.

Adult↗

Diagnostic value of 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) in patients with chest pain. Comparison with rest-stress 99mTc-tetrofosmin SPECT and coronary angiography.

BACKGROUND: Basic and clinical studies have indicated that 15-(p-[(123)I] iodophenyl)-3-(R, S) methylpentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) can identify ischemic myocardium without evidence of myocardial infarction by the regional decline of tracer uptake. The present study compared BMIPP SPECT with rest-stress myocardial perfusion imaging (MPI) findings and coronary angiography (CAG) in 150 patients with acute chest pain. METHODS AND RESULTS: Patients with acute chest pain who underwent all of the following tests were selected: MPI at rest-stress, BMIPP SPECT at rest and CAG. Organic coronary artery stenosis (>or=75%) was observed in 46 patients, 27 patients had total or subtotal coronary occlusion by spasm in the spasm provocation test on CAG and the remaining 77 patients had no significant coronary artery stenosis or spasm. The sensitivity of BMIPP at rest to detect organic stenosis was significantly higher (54%) than that of rest-MPI (33%, p<0.005), but lower than that of stress-MPI (76%, p=0.05). The sensitivity of BMIPP at rest to detect spasm was significantly higher (63%) than that of both rest-MPI (15%; p<0.001) and stress-MPI (19%; p<0.001). Overall, the sensitivity of BMIPP at rest to detect both organic stenosis and spasm was significantly higher (58%) than that of rest-MPI (26%; p<0.001), despite having no significance with that of stress-MPI (55%). The specificity was not significantly different among the three imaging techniques. CONCLUSION: Resting BMIPP SPECT is an alternative method to stress MPI for identifying patients with not only organic stenosis but also spasm without the need for a stress examination.

Aged↗

REST in good times and bad: roles in tumor suppressor and oncogenic activities.

The repressor element 1 (RE-1)-silencing transcription factor (REST), also known as the neuron-restrictive silencer factor (NRSF), was originally discovered as a transcriptional repressor of a large number of primarily terminal neuronal differentiation genes in nonneuronal cells and neural stem cells (NSCs). Although REST is expressed in NSCs, its transcription is generally blocked as NSCs undergo differentiation, and it is rarely expressed in terminally differentiated neurons. In support of its function as a transcriptional repressor, REST was found to contain a DNA-binding domain and two repressor domains. The repressor domains were found to associate, directly or indirectly, with a large number of cellular repressor complexes. Thus, REST was considered a major epigenetic regulator controlling chromatin modification. However, REST is expressed in some differentiated neurons, and when bound to a double-stranded small RNA, REST was later found to also function as an activator of its same target neuronal differentiation genes in NSCs. In addition, REST has been found to regulate an evolving array of genes and cellular functions, making it a biological enigma. For example, REST was recently found to have a seemingly paradoxical role in both tumor suppressor activity and oncogenic activity. Current evidence suggests that the diverse cellular context generated by intrinsic factors in the cell, the amount of REST protein present in the cell, the affinity of the REST protein for its specific target gene, and the cellular niche dictate such behavior.

Animals↗

Haemodynamic effect of atrail triggered versus fixed rate pacing at rest and during exercise in complete heart block.

The central haemodynamics at rest and during exercise have been studied in 25 patients with complete AV block who were treated with fixed rate (FRP) and atrial triggered pacemakers (ATP). The aim of the investigation has been to study the effect of a synchronized atrial contraction for the filling of the ventricles and for the cardiac output (Q). Pressures and Q have been determined during heart catheterization. The P wave for triggering the atrial synchronized pacemaker has been obtained with an electrode in close contact with the atria, introduced by means of mediastinoscopy. The study consists of two series. In the first series (12 patients) the central haemodynamics were recorded with each patient connected first the FRP (about 70 impulses/min) and later to the ATP. Most patients were studied both at rest and during exercise, the work loads being identical with both types of pacemakers. Q at rest is 10% higher with ATP (p less than 0.02) than with FRP and during exercise 20% higher with ATP (p less than 0.01). Stroke volume (SV) at rest is equal with both types of pacemakers, but significantly larger with FRP during work (p less 0.001). The left ventricular (LV) filling pressure is significantly lower (p less than 0.01) with ATP at rest, but not during exercise (p less than 0.8). In the second series 13 patients were studied at rest and during exercise. The recordings of pressures and Q were first performed with the patient on ATP. After 30 min rest an identical study was performed with the patient connected to FRP, the rate of which was matched (FRPm) to that previously recorded with ATP. Q at rest is 18% higher (p less than 0.01) with ATP than with FRPm and during work 8% higher (p less than 0.05) with ATP. SV at rest is significantly larger (p less than 0.01) with ATP than with FRPm, whereas during exercise no significant difference is observed between the two types of pacemakers. LV filling pressure at rest is significantly lower on the 5% level with ATP; during exercise no significant difference is observed. The investigation shows that in many patients, especially younger ones, treatment with ATP makes it possible to obtain a larger Q during exercise, and thus to increase the oxygen transporting capacity of the circulation. This benefical effect may be more pronounced in patients with low compliance of the ventricular myocardium.

Adult↗

The agreement between measured and predicted resting energy expenditure in patients with pancreatic cancer: a pilot study.

OBJECTIVE: To compare measured resting energy expenditure to resting energy expenditure predicted from eight published prediction equations in a sample of patients with pancreatic cancer. DESIGN: Cross-sectional study. SETTING: Ambulatory patients of a tertiary private hospital. PARTICIPANTS: Eight patients with pancreatic cancer (5 males, 3 females; age: 62.0+/- 5.2 years; BMI: 24.4+/- 3.2 kg/m2; weight loss: 12.1+/- 6.0%; mean+/- SD). METHODS: Resting energy expenditure was measured using indirect calorimetry and predicted from eight published prediction methods (Harris-Benedict with no injury factor, Harris-Benedict with 1.3 injury factor, Schofield, Owen, Mifflin, Cunningham, and Wang equations and the 20 kcal/kg ratio). Body composition was assessed by deuterium oxide dilution technique. Statistical analysis was performed by using the method of Bland and Altman, and the Student's t-test. RESULTS: The Harris-Benedict equations with an injury factor of 1.3 resulted in a significantly higher mean predicted resting energy expenditure compared to measured resting energy expenditure, while there was no significant difference between mean measured and predicted resting energy expenditure and the other 7 methods. At an individual level, the limits of agreement are wide for all equations. The best combination of low bias and narrowest limits of agreement was observed in the prediction of resting energy expenditure from the Wang equation (based on fat free mass) and the Harris-Benedict equation (based on weight and height). CONCLUSION: At a group level, there is agreement between mean measured and predicted resting energy expenditure with the exception of the Harris-Benedict equation with an injury factor of 1.3. The results of this pilot study suggest that, for an individual, the limits of agreement are wide, and clinically important differences in resting energy expenditure would be obtained. Clinicians need to be aware of the limitations of the use of resting energy expenditure prediction equations for individuals.

Aged↗

Bed rest for acute low back pain and sciatica.

BACKGROUND: Low back pain is a common reason for consulting a general practitioner, and advice on daily activities constitutes an important part in the primary care management of low back pain. OBJECTIVES: To assess the effects of bed rest for patients with acute low back pain or sciatica. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trial register, Cochrane Controlled Trials Register, MEDLINE, Embase, Sport, Scisearch, and reference lists of relevant articles. We also contacted authors of relevant articles. Date of the most recent searches: December 1998. SELECTION CRITERIA: We included all randomised studies or quasi randomised studies where at least one comparison group of adult patients with acute low back pain with or without radiation of pain below the knee was advised to rest in bed for at least two days and one group was not, or where comparison groups were advised to stay in bed for different lengths of time. The main outcomes of interest were pain, functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to obtain missing information. MAIN RESULTS: Nine trials with a total of 1435 patients were included. Five trials met all four validity criteria and were assessed to have low risk of bias, while four trials were assessed to have moderate to high risk of bias. Four trials compared bed rest with advice to stay active, and overall the results were heterogeneous. Overall results from two high quality studies indicate no difference in pain intensity at three weeks follow-up [Standardized Mean Difference 0.0 (95%CI: -0.3, 0.2)], and a small difference in functional status in favour of staying active [Weighted Mean Difference 3.2 (on a 0-100 scale) (95%CI 0.6, 5.8)]. Two high quality trials reported no differences in pain intensity between two to three days of bed rest and seven days of bed rest. Another two high-quality trials found no differences between bed rest and exercises in pain intensity or functional status. REVIEWER'S CONCLUSIONS: Bed rest compared to acvice to stay active will at best have small effects, and at worst might have small harmful effects on acute LBP. Differences in effects of advice to stay in bed compared with advice to stay active are small for patients with low back pain with or without sciatica. There is not an important difference in the effects of bed rest compared with exercises in the treatment of acute low back pain, or seven days compared with two to three days of bed rest in patients with low back pain of different duration with and without radiating pain.

Acute Disease↗

Rest and redistribution thallium-201 myocardial scintigraphy to predict improvement in left ventricular function after coronary arterial bypass grafting.

To examine the value of rest and redistribution thallium-201 imaging in predicting improvement in left ventricular (LV) ejection fraction (EF) after coronary artery bypass grafting (CABG), 26 patients with coronary artery disease (CAD) and abnormal LV function were studied. Nineteen patients had pathologic Q waves preoperatively. Rest and redistribution thallium-201 images and radionuclide ventriculograms were obtained before and after CABG, and the thallium scintigrams were evaluated both quantitatively and qualitatively. The patients were divided according to the preoperative thallium scintigrams into 2 groups: Group I (16 patients) had either normal resting thallium-201 images or reversible resting perfusion defects, and Group II (10 patients) had fixed resting perfusion defects. The resting EF was less than 50% preoperatively in all patients. Fourteen patients (54%) showed improvement in EF postoperatively. Three patients (2 in Group I and 1 in Group II) showed new postoperative perfusion defects, and none of the 3 showed improvement in LV function. Of the remaining 14 patients in Group I, 12 (86%) showed improvement in LV function, compared with 2 of 9 patients in Group II (p less than 0.01). Improvement in LV function was observed in 8 of the 19 patients (42%) with abnormal Q waves. Nitroglycerin intervention radionuclide ventriculograms were obtained in 20 patients before CABG. Of the 6 patients who showed improvement in LV function with nitroglycerin, 4 also showed improvement postoperatively. Postoperative improvement in LV function was also observed in 6 of the 14 patients who did not improve with nitroglycerin. Thus, rest and redistribution thallium imaging is useful in identifying patients whose LV function will improve after CABG. Normal rest thallium-201 images or reversible resting defects correctly identified 12 of 14 patients (86%) who showed improvement in LV function postoperatively. Nitroglycerin-intervention ventriculography and abnormal Q waves were less useful in this differentiation.

Adult↗

Resting tremor only: a variant of Parkinson's disease or of essential tremor.

Resting tremor is one of the characteristic features of Parkinson's disease. However, there are a number of patients who typically have resting tremor alone for at least 5 years without development of other parkinsonian signs or symptoms. The etiology of an isolated resting tremor is still obscure. Recently, positron emission tomography was used to study these patients with isolated resting tremor, and demonstrated a markedly decreased striatal uptake of fluoro-dopa to the range of Parkinson's disease. These findings suggested the existence of a separate subtype, namely, tremulous Parkinson's disease with a manifestation of resting tremor alone. In order to confirm the existence of this subgroup of tremulous Parkinson's disease and further investigate its morphological changes and the usefulness of magnetic resonance imaging, we collected 5 patients who typically have resting tremor for at least 8 years in the absence of other features of Parkinson's disease. MRI was performed and the results of the images showed typical findings of Parkinson's disease with smudging or decreased distance between substantia nigra and red nucleus. Quantitative analysis also demonstrated a significant decrease of the above-noted distance when the resting tremor group was compared to the essential tremor group. Therefore, patients with an isolated resting tremor can have morphological abnormalities in addition to functional disturbances shown by positron emission tomography. To our knowledge, this is the first paper to report that resting tremor is a variant of Parkinson's disease rather than essential tremor, by using a double-blind method, with magnetic resonance imaging to support.

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