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Randomized, controlled trial of biofeedback with anal manometry, transanal ultrasound, or pelvic floor retraining with digital guidance alone in the treatment of mild to moderate fecal incontinence.

BACKGROUND: A prospective, three-armed, randomized, controlled trial was performed to assess whether pelvic floor exercises with biofeedback using anal manometry or transanal ultrasound are superior to pelvic floor exercises with feedback from digital examination alone in terms of continence, quality of life, physiologic sphincter strength, and compliance. Its secondary objectives were to assess whether there are any differences in these outcomes between biofeedback with transanal ultrasound vs. anal manometry and to correlate the physiologic measures with clinical outcome. METHODS: One hundred twenty patients with mild to moderate fecal incontinence were randomized into one of three treatment groups: biofeedback with anal manometry, biofeedback with transanal ultrasound, or pelvic floor exercises with feedback from digital examination alone. Commencing one week after an initial 45-minute assessment session, patients attended monthly treatments for a total of five sessions. Each session lasted 30 minutes and involved sphincter exercises with biofeedback that involved instrumentation or digital examination alone, and patients were encouraged to perform identical exercises twice per day between outpatient visits. RESULTS: One hundred two patients (85 percent) completed the four-month treatment program. Across all treatment allocations, patients experienced modest but highly significant improvements in all nine outcome measures during treatment, with 70 percent of all patients perceiving improvement in symptom severity and 69 percent of patients reporting improved quality of life. With the possible exception of isotonic fatigue time, there were no significant differences between the three treatment groups in compliance, physiologic sphincter strength, and clinical or quality-of-life measures. Correlations between physiologic measures and clinical outcomes were much stronger with ultrasound-based measures than with manometry. CONCLUSIONS: Although patients in this study who completed pelvic floor exercises with feedback from digital examination achieved no additional benefit from biofeedback and measurement with transanal ultrasound or manometry, it may be that the guidance received through digital examination alone offered patients in the pelvic floor exercise group an effective biofeedback mechanism. Contrary to our hypothesis, the use of transanal ultrasound offered no benefit over manometry, but the use of ultrasound for isotonic fatigue time and isometric fatigue contractions provided potentially important physiologic measures that require further study. This study has confirmed, through a large sample of patients, that pelvic floor retraining programs are an effective treatment for improving physiologic, clinical, and quality-of-life parameters in the short term.

Aged↗

Contractile response of rabbit dilator pupillae muscle to isotonic high K or norepinephrine, and Ca movement.

Isotonic 80 mM K and norepinephrine contracted the isolated dilator pupillae muscle of the rabbit. Norepinephrine-induced contraction was inhibited by papaverine, but not by Ca blockers, while K-induced contraction was abolished by removing Ca from the bathing fluid but there was a residual response to norepinephrine in Ca-free solution. These results suggest that, in the rabbit dilator pupillae muscle, K-induced contraction is mainly attributable to the increase of Ca influx, while norepinephrine-induced contraction is mainly due to the facilitation of release of intracellularly sequestered Ca.

Animals↗

The response to ischemia in blood perfused vs. crystalloid perfused isolated rat heart preparations.

With a research hypothesis that the behavior of blood perfused hearts was different from that of crystalloid perfused hearts, we tested the null hypothesis that the functional and metabolic status of blood-perfused (paracorporeal oxygenation) and Krebs-Henseleit (bubble oxygenation) perfused Langendorff isolated rat hearts is the same before, during and after global myocardial ischemia. Thirty isolated rat hearts were studied under identical conditions except that in equal numbers they were randomly assigned to either blood or crystalloid perfusion. In the blood perfused and crystalloid perfused hearts subjected to 22 min of normothermic ischemia and 30 min of reperfusion, mean systolic recovery was 72 +/- 3.9% (S.E.) and 20 +/- 10% (P = 0.001), respectively; coronary resistance increased 21 +/- 16% and 158 +/- 27% (P = 0.0003) (unadjusted for viscosity); mean water content after reperfusion was 82.0 +/- 0.43% and 86.7 +/- 0.42% (P < 0.0001), ATP content was 8.4 +/- 1.9 and 4.3 +/- 0.5 mumol/g dry wt (P = 0.08), and energy charge was 0.74 +/- 0.114 and 0.59 +/- 0.048 (P = 0.3). A major qualitative difference during reperfusion was spontaneous relaxation of contracture and rapid resumption of sinus rhythm in blood perfused hearts, in contrast to continued contracture and rise in intraventricular pressure in 9 of 10 crystalloid perfused hearts. One crystalloid perfused heart did not develop contracture, and its phenomena during reperfusion were similar to those of blood perfused hearts. The data support the research hypothesis, and suggest caution in extrapolating to blood perfused systems inferences from crystalloid perfused models. Better preservation of reactive hyperemia early in reperfusion may explain the better performance of blood perfused hearts.

Adenosine Triphosphate↗

Absence of calcium paradox in the cardiac ventricle of the Atlantic hagfish (Myxine glutinosa).

Spontaneously beating strips of the cardiac ventricle of the cyclostome Myxine glutinosa were characterized with respect to dependence on extracellular calcium for the cardiac contractility at 8 degrees C. The force developing (Tmax) was reduced by 20-50% when exposed to calcium-free medium (+/- 10(-3)M EDTA) for 15-60 min. Return to normal Myxine Ringer (4.5 mM Ca2+) resulted in 120-130% recovery to Tmax without change in resting tension. These experiments show that the heart of this primitive vertebrate, analogous to that of other poikilotherms, does not display the "Ca-paradox" phenomenon. Being relatively insensitive to changes in extracellular Ca2+ the Myxine myocardium differs from that in most poikilotherms in other respects, e.g. in the mechanisms regulating beat to beat changes in intracellular Ca2+.

Animals↗

Chronic hypokalemia and the left ventricular responses to epinephrine and preload.

The effects of moderate, chronic (5 days) potassium depletion on cardiac function were assessed in 14 normokalemic and 13 hypokalemic open chest, anesthetized dogs. Cardiac responses to intravenous bolus injection of 2.5 micrograms/kg body weight epinephrine (10 normokalemic and 11 hypokalemic dogs) and to rapidly increased preload (8 dogs in each group) were evaluated. Hypokalemic dogs received a low potassium diet plus chlorthalidone. Plasma potassium levels were lower (p less than 0.001) in the hypokalemic dogs (3.2 +/- 0.1 mEq/liter [mean +/- SEM]) than in the normokalemic dogs (4.1 +/- 0.1). The inotropic response to epinephrine was lower in hypokalemic than in normokalemic dogs, the response of the maximal rate of rise of left ventricular pressure was 20% greater (p less than 0.03) and the response of the peak rate of change of ejection power was 60% greater in the normokalemic dogs. The relaxation response to epinephrine (the maximal rate of fall of left ventricular pressure) was 33% lower (p less than 0.02) in hypokalemic dogs. Responses to rapid volume expansion were impaired by hypokalemia; maximal stroke volume index was 31% lower (p less than 0.01), maximal cardiac index was 26% lower (p less than 0.01) and the peak response to the maximal rate of filling was 51% lower (p less than 0.01). There were no differences in basal cardiac function. Therefore, modest potassium depletion within the clinical range impaired the contractile and relaxation responses to epinephrine and preload and impaired rapid filling.

Animals↗

Improvement in functional recovery of the isolated guinea pig heart after hyperkalemic reperfusion with adenosine.

The aim of this study was to examine the effect of initial hyperkalemic reperfusion (HKR), with and without added adenosine, on coronary flow, myocardial function, and endothelium-dependent and endothelium-independent coronary vascular function. Cardioplegic arrest was induced in 40 isolated guinea pig hearts by infusing oxygenated cardioplegic (high in potassium ion) Krebs solution for 5 minutes. Hearts were then stored at room temperature for 3.5 hours. On reperfusion, hearts were divided into four groups of 10 hearts each: control, reperfusion with regular Krebs solution (4.6 mmol/L potassium chloride); base hyperkalemic reperfusion, initial reperfusion with 37 degrees C oxygenated, cardioplegic Krebs solution for 5 minutes; hyperkalemic reperfusion with addition of 1 mmol/L adenosine during HKR; and hyperkalemic reperfusion with addition of 5 mmol/L adenosine. Coronary reserve (adenosine bolus 2 mmol/L) and responses to acetylcholine (1 mumol/L) and nitroprusside (100 mumol/L) were examined before and after ischemia and reperfusion. Flow did not return to preischemic values in any group after reperfusion. Adenosine treatment during initial reperfusion increased coronary flow (percentage of baseline +/- standard error of the mean) from 57% +/- 4% in control and 45% +/- 3% in hearts with hyperkalemic reperfusion to 79% +/- 3% and 83% +/- 5% in hearts with hyperkalemic reperfusion also treated with, respectively, 1 mmol/L adenosine and 5 mmol/L adenosine (p < 0.05). At 30 and 60 minutes of reperfusion, however, flow remained elevated only in the group treated with 5 mmol/L adenosine. Coronary reserve and responses to acetylcholine and nitroprusside were equivalently depressed in all groups after reperfusion. Recovery of left ventricular systolic and diastolic function was improved in all groups after hyperkalemic reperfusion (54% +/- 4% of preischemic value) compared with control (39% +/- 3%), and recovery was further enhanced in the group treated with 5 mmol/L adenosine (60% +/- 4%). In this ex vivo model, hyperkalemic reperfusion improved myocardial function after cardioplegic arrest and the addition of 5 mmol/L adenosine improved coronary flow. Adenosine may counteract the potassium chloride-induced vasoconstriction that occurs during hyperkalemic reperfusion and may thus improve coronary flow and myocardial function. Postischemic depression of endothelium-dependent or endothelium-independent vascular functions, however, was not alleviated by hyperkalemic reperfusion with or without adenosine.

Acetylcholine↗

Preservation of bladder tissue in different solutions for varying times.

OBJECTIVES: To evaluate three popular storage media and the effect of 24-hour cold storage on bladder tissue. METHODS: Guinea pig bladders were stored in three solutions: UW solution (a media used for transplant organs), Reznikoff solution [cell culture medium], and Krebs' solution with and without aeration. RESULTS: Cell potassium and sodium concentrations and total tissue water (a measurement of cell swelling) are important parameters for evaluating tissue damage. Reznikoff solution and Krebs' solution without gases maintained tissues for 24 hours with the least tissue damage; these solutions require no special equipment or attention. Twenty-four hour uniterrupted aeration of Krebs' solution caused the greatest degree of cell swelling with possible redistribution of receptors and required adjustment and regulation of the preservation apparatus. UW solution induced dehydration of cells, required the longest recovery period after cold storage, and is far more expensive than the other solutions. CONCLUSIONS: Reznikoff solution caused consistent relative changes in smooth muscle receptors and was superior to aerated Krebs' and UW solutions for 24-hour bladder tissue storage. It is unnecessary to aerate Krebs' solution during 24-hour cold storage.

Adenosine↗

Contractile effects of 5-hydroxytryptamine and 5-carboxamidotryptamine in the equine jejunum.

The use of human prokinetic drugs in colic horses leads to inconsistent results. This might be related to differences in gastrointestinal receptor populations. The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the equine mid-jejunum were therefore studied. Longitudinal muscle preparations were set up for isotonic measurement. 5-HT induced tonic contractions with superimposed phasic activity; these responses were not influenced by tetrodotoxin and atropine, suggesting a non-neurogenic, non-cholinergic pathway. The 5-HT receptor antagonists GR 127935 (5-HT(1B,D)), ketanserin (5-HT(2A)), SB 204741 (5-HT(2B)), RS 102221 (5-HT(2C)), granisetron (5-HT(3)), GR 113808 (5-HT(4)) and SB 269970 (5-HT(7)) had no influence on the 5-HT-induced response; the 5-HT(1A) receptor antagonists NAN 190 (pK(b)=8.13+/-0.06) and WAY 100635 (pK(b)=8.69+/-0.07), and the 5-HT(1,2,5,6,7) receptor antagonist methysergide concentration-dependently inhibited the 5-HT-induced contractile response. The 5-HT(1,7) receptor agonist 5-carboxamidotryptamine (5-CT) induced a contractile response similar to that of 5-HT; its effect was not influenced by tetrodotoxin and atropine, and SB 269970, but antagonised by WAY 100635. 8-OHDPAT, buspiron and flesinoxan, which are active at rat and human 5-HT(1A) receptors, had no contractile influence. These results suggest that the contractile effect of 5-HT in equine jejunal longitudinal muscle is due to interaction with muscular 5-HT receptors, which cannot be characterised between the actually known classes of 5-HT receptors.

Animals↗

The effect of oxytocics on the "Ca-deficient" uterus. A measure of oxytocic potency.

If the excised, parturient rabbit uterus is repeatedly treated with a Krebs solution free from Ca, its tension in a tetanus drops gradually, and in 15 to 30 minutes becomes zero. We call such a uterus "Ca-deficient." The uterus in this condition has a high threshold, it is non-propagating, "inexcitable," fails to respond to oxytocics in a characteristic fashion, but retains maximum contractility. As Ca is gradually restored to the Krebs, these lost qualities return in a graded fashion and tension of the tetanized uterus becomes a log function of the [Ca]. If the [Ca] is kept low, i.e. 1/10 to 1/20 of the normal, tetanic tension is small but steady, and the preparation offers a full scale of tension increment for the measurement of oxytocic potency. Keeping the stimulus and the [Ca] constant, excitability (measured by tension increment) is a log function of the drug concentration. The recovery of excitability by restoring Ca to the Ca-deficient uterus is strongly temperature-dependent. The Ca-deficient uterus is a useful preparation for the study of the mechanism of regulation. When its excitability is partially recovered by Ca, the electrically stimulated uterus becomes an excellent tool for the quantitative measurement of oxytocic potency.

Animals↗

A study on the electrical resistance of the frog sartorius muscle.

Four different methods of measuring the resistance of a muscle fiber have been applied to the frog sartorius muscle. The methods, in which the resistance of the microelectrode entered the calculation of the effective resistance of the fiber, resulted in values which were 8 times higher than the resistance values obtained with methods independent of the electrode resistance. A simple cable model of a muscle fiber could not account for the discrepancy in the effective resistance found in these measurements; therefore, an enlarged cable model for a muscle fiber has been proposed, and its biological implications have been discussed. The effective resistance (measured with the two different groups of methods) decreased when the potassium concentration in the bath increased. Using the proposed enlarged cable model for the interpretation of these results, it is shown that not only the membrane resistance but also the myoplasmic resistance decreases with an increasing potassium concentration in the Ringer solution.

Animals↗

Effects of quadriceps femoris muscle strengthening on crouch gait in children with spastic diplegia.

BACKGROUND AND PURPOSE: Despite evidence of weakness in children with cerebral palsy, the use of strength training in this population remains controversial. SUBJECTS: Fourteen children with spastic diplegia, ranging in age from 6 to 14 years (X = 9.1, SD = 2.5), participated in a bilateral quadriceps femoris muscle strengthening program. METHODS: The children exercised three times per week for 6 weeks using ankle weights at loads of approximately 65% of each child's maximum isotonic force production. The maximal voluntary contraction of the quadriceps femoris muscles was measured before, at the midpoint of, and immediately following the exercise program at 30, 60, and 90 degrees of knee flexion. Gait analyses were performed before and after the strengthening program to determine whether quadriceps femoris muscle strengthening influenced gait. RESULTS: Children with spastic diplegia can increase quadriceps femoris muscle strength through heavy resistance exercise. Repeated-measures analysis of variance and multivariate analysis of variance procedures were used to assess changes in force and in gait variables. Improvement in the degree of crouch at initial floor contact at the freely selected speed and an increase in stride length at free and fast speeds were found. CONCLUSION AND DISCUSSION: These findings suggest that resistance exercise is an effective treatment strategy and as such should be considered as one component in the habilitation of children with cerebral palsy.

Adolescent↗

Metabolic factors involved in regulation of muscle blood flow.

Muscles with various compositions of muscle fibers show a different degree of functional hyperemia. This can be caused by either a different pattern of vascular recruitment, a release of various metabolites, or a heterogeneous sensitivity of vessels in different muscles to individual metabolites. The possible involvement of hypoxia, adenosine, ATP, lactate, pH, hyperosmolarity, potassium, and inorganic phosphate in functional hyperemia is discussed. It is concluded, on the basis of the data from the literature as well as on that of our own experiments, that potassium and inorganic phosphate are equally involved in functional hyperemia in mixed muscles during short-lasting isotonic or isometric rhythmic or tetanic contractions. Potassium seems to be more important in long-lasting contractions, whereas inorganic phosphate seems to be more important in muscles with a high proportion of oxidative fibers. Other factors, such as low pH, might enhance the vasodilating potency of phosphate, and adenosine seems to be involved only to a small extent.

Adenosine↗

Hypertonic saline dextran resuscitation fails to improve cardiac function in neonatal and senescent burned guinea pigs.

Our previous studies suggested that the greater diminution in burn-induced cardiac contractile function which occurs in young and elderly subjects compared with adult subjects is related to differences in intracellular calcium availability to the myofilaments. We recently showed that improved cardiac function after hypertonic saline dextran (HSD) resuscitation from burn injury in adults was related to enhanced intracellular calcium content. In the study presented here, 126 hearts isolated from neonatal, adult, and senescent guinea pigs were used to evaluate age-related differences in cardiac contractile response to HSD resuscitation from burn injury. Scald burn was induced in 30 adult, 18 neonatal, and 30 senescent guinea pigs; within each age group, half of the burned animals were resuscitated with lactated Ringer's (Parkland formula, 4 mL/kg/% burn for 24 hours); half received an initial bolus of HSD (4 mL/kg, IV) plus lactated Ringer's (1 mL/kg/% burn for 24 hours). An additional 16 animals from each age group served as sham burn controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Protein kinase C inhibition improves ventricular function after thermal trauma.

OBJECTIVE: To examine the effect of protein kinase C (PKC) inhibition on cardiac performance and intracellular Ca2+ homeostasis. DESIGN: Previous studies have shown that trauma impairs cardiac mechanical function, and recent studies suggest that PKC activation and subsequent perturbations in Ca2+ sequestration/release contribute to this cardiac dysfunction. In this study, anesthetized guinea pigs were given third-degree scald burns over 43 +/- 1% of the total body surface area and resuscitated with lactated Ringer's solution (LR) 4 mL/kg per percent of burn, Parkland formula. Animals with sham burns served as controls (n = 18). Burns were randomly divided into two groups: LR alone (N = 18) or LR + PKC inhibitor, calphostin C (0.1 mg/kg, intravenous bolus), given 30 minutes and 3, 6, and 21 hours after burn (n = 18). MATERIALS AND METHODS: Cardiac function was assessed by Langendorff preparation 24 hours after burn in 8 to 12 animals per group. Intracellular calcium concentration ([Ca2+]i) was measured in cardiac myocytes (collagenase digestion) from additional animals in each experimental group (n = 5-9 per group) after Fura-2 AM loading of myocytes; fluorescence ratios were measured with a Hitachi spectrofluorometer. RESULTS: Cardiac dysfunction occurred 24 hours after burn in LR burns as indicated by lower left ventricular pressure and a reduced rate of left ventricular pressure rise and fall, +/-dP/dt (61 +/- 3 mm Hg, 1,109 +/- 44 mm Hg/s, and 880 +/- 40 mm Hg/s, respectively) compared with values measured in sham-burned animals (86 +/- 2 mm Hg, 1365 +/- 43 mm Hg/s, and 1183 +/- 30 mm Hg/s, respectively; p < 0.05). Ventricular function curves confirmed significant postburn contractile depression despite aggressive fluid resuscitation. Cardiac injury in burned animals was indicated by an increase in perfusate creatine kinase and lactate dehydrogenase, and Ca2+ dyshomeostasis was confirmed by increased myocyte [Ca2+]i (sham 151 +/- 6 vs. burn 307 +/- 20 nmol/L, p < 0.05). PKC inhibition improved all indices of cardiac performance, producing left ventricular pressure (82 +/- 3 mm Hg), +/-dP/dt (1,441 +/- 48 and 1,294 +/- 32 mm Hg/s), and left ventricular function curves that were comparable with those of sham-burned animals. In addition, [Ca2+]i in calphostin-treated burned animals (154 +/- 11 nmol/L) was identical to values in sham-burned animals. CONCLUSION: Our data suggest that PKC may serve as a final common pathway in signal transduction events mediating postburn cardiac dysfunction.

Animals↗