Predictors and moderators of the response of adults with intellectual disabilities and depression to behavioural activation and guided self-help therapies.

BACKGROUND: No previous studies have reported predictors and moderators of outcome of psychological therapies for depression experienced by adults with intellectual disabilities (IDs). We investigated baseline variables as outcome predictors and moderators based on a randomised controlled trial where behavioural activation was compared with guided self-help. METHODS: This study was an exploratory secondary data analysis of data collected during a randomised clinical trial. Participants (n = 161) were randomised to behavioural activation or guided self-help and followed up for 12 months. Pre-treatment variables were included if they have previously been shown to be associated with an increased risk of having depression in adults with IDs or have been reported as a potential predictor or moderator of outcome of treatment for depression with psychological therapies. The primary outcome measure, the Glasgow Depression Scale for Adults with Learning Disabilities (GDS-LD), was used as the dependant variable in mixed effects regression analyses testing for predictors and moderators of outcome, with baseline GDS-LD, treatment group, study centre and antidepressant use as fixed effects, and therapist as a random effect. RESULTS: Higher baseline anxiety (mean difference in outcome associated with a 1 point increase in anxiety 0.164, 95% confidence interval [CI] 0.031, 0.297; P = 0.016), lower performance intelligence quotient (IQ) (mean difference in outcome associated with a 1 point increase in IQ 0.145, 95% CI 0.009, 0.280; P = 0.037) and hearing impairment (mean difference 3.449, 95% CI 0.466, 6.432; P = 0.024) were predictors of poorer outcomes, whilst greater severity of depressive symptoms at baseline (mean difference in outcome associated with 1 point increase in depression -0.160, 95% CI -0.806, -0.414; P < 0.001), higher expectation of change (mean difference in outcome associated with a 1 point increase in expectation of change -1.013, 95% CI -1.711, -0.314; p 0.005) and greater percentage of therapy sessions attended (mean difference in outcome with 1 point increase in percentage of sessions attended -0.058, 95% CI -0.099, -0.016; P = 0.007) were predictors of more positive outcomes for treatment after adjusting for randomised group allocation. The final model included severity of depressive and anxiety symptoms, lower WASI performance IQ subscale, hearing impairment, higher expectation of change and percentage of therapy sessions attended and explained 35.3% of the variance in the total GDS-LD score at 12 months (R2  = 0.353, F4, 128  = 17.24, P < 0.001). There is no evidence that baseline variables had a moderating effect on outcome for treatment with behavioural activation or guided self-help. CONCLUSIONS: Our results suggest that baseline variables may be useful predictors of outcomes of psychological therapies for adults with IDs. Further research is required to examine the value of these potential predictors. However, our findings suggest that therapists consider how baseline variables may enable them to tailor their therapeutic approach when using psychological therapies to treat depression experienced by adults with IDs.

Impairment of the actin-myosin interaction in permeabilized cardiac trabeculae after chronic doxorubicin treatment.

The development of chronic cardiotoxicity in cancer patients treated with doxorubicin (DOX) and other anthracycline antineoplastic agents is a major dose-limiting factor. In a previous study, we demonstrated an acute effect of anthracyclines on the actin-myosin contractile system. Here, we report chronic effects of DOX both on the contractile system and on the function of the sarcoplasmic reticulum (SR). Male Wistar rats were treated with DOX (2 mg/kg, i.v., once a week for 4 weeks), whereas control rats received equal volumes of saline. Right ventricular trabeculae were isolated and skinned by exposure to Triton X-100 or saponin at 1, 2, 4, and 6 weeks after the final DOX administration. The maximal tension of trabeculae was similar between DOX-treated and control animals at 1 week posttreatment. At 2, 4, and 6 weeks posttreatment, the maximal tension of trabeculae of DOX-treated animals was significantly decreased by 27, 32, and 37%, respectively (P < 0.01). The rigor tension in trabeculae of DOX-treated animals was similar at 1 week posttreatment but significantly decreased at 2, 4, and 6 weeks posttreatment (by 25, 25, and 37%, respectively; P < 0.01). The ratio between rigor tension and maximal tension was significantly higher in DOX-treated groups as compared to controls (0.39 +/- 0.01 and 0.36 +/- 0.01; P < 0.05). Calcium sensitivity of DOX-treated preparations was significantly decreased as compared to controls (5.59 +/- 0.02 and 5.65 +/- 0.01; P < 0.05), whereas no effects were found on the cooperativity of the regulatory proteins, as measured by the Hill coefficient. The calcium release function of the SR, measured by caffeine (25 mM) stimulation in saponin-skinned trabeculae, was the same in DOX-treated and control groups at all posttreatment periods. The results of the present study show that long-term DOX treatment causes substantial impairment of the cross-bridge interaction in skinned trabeculae, which is reflected by a progressive attenuation of the contractile performance. The function of the SR, however, remains unaffected by DOX treatment in our preparations. The direct effect of chronic DOX treatment on the actin-myosin system provides an additional mechanism through which anthracyclines exert their cardiotoxic effects and may facilitate the development of cardioprotective strategies.

The lived experience of women subjected to domestic violence and abuse.

The number of incidents of domestic violence appears to be continually on the increase. Domestic violence and repeated victimisation and offending can even give rise to fatality. Evaluation of the quality of service delivery and understanding of domestic violence by community members and health care workers show poor results with some people still clinging to myths coming from cultural beliefs. The goal of this article is to explore and describe the lived experience of women subjected to domestic violence and abuse; and to make recommendations for nursing practice, nursing education and nursing research to support women who were subjected to domestic violence and abuse, in facilitating their mental health and optimising their ability to terminate the abusive situation. The framework of the Theory for Health Promotion in Nursing (Rand Afrikaans University, 2000) was used. A qualitative, explorative, descriptive and contextual research design and in-depth, semi-structured, qualitative research interviews were used. Guba's model of trustworthiness (Poggenpoel, 1998: 348-350) was applied. Guba's model for trustworthiness was used (Poggenpoel, 1998: 348-350) Data analysis was done according to Tesch's method (Poggenpoel, 1998: 343-352). The target population of this study was white women in Middelburg, Mpumalanga Province, that experienced abuse for at least the last year and were still married to or in the process of divorcing the abuser. The researcher used a sample of nine participants of which one was involved in the pilot study.

The combined influence of the stimulus frequency of the vagal nerves and the atrial stimulus interval on the atrioventricular conduction time.

The way in which the A-V node adapts its conduction time to stepwise alterations of atrial stimulation rates was studied under different conditions of vagal nerve activity (open chest, anaesthetised rabbit). Increase of stimulation rate induced oscillatory adaptation to a longer conduction time. Decrease caused shorter conduction times without oscillation. The time constant did not differ. Oscillation amplitude and time constants were markedly influenced by vagal activity. The observed phenomena can be explained on the basis of a time and voltage dependent K+ conductance.

A note on the phase-plane technique representation of cardiac action potentials.

In this study the applicability of the phase-plane technique for interpreting membrane properties of cardiac cells in a two-dimensional structure is discussed. The conditions are derived for which the effects of two-dimensionality of a sheet can be neglected and for which the one-dimensional phase-plane technique for estimation of the membrane current densities remains valid. The usual phase-plane technique appears to be applicable to nodal and atrial tissue.

Immediate effects of diastolic loading variations on the left ventricular inotropic state in open chest dogs.

The influence of left ventricular filling and variations in end diastolic volume on cardiac performance was studied in the intact dog heart. Left ventricular filling volumes and stroke volumes were calculated on a beat to beat basis from measurements of natural mitral inflow and aortic outflow obtained by electromagnetic flow sensors. Instantaneous controlled modifications of end diastolic volume were performed through a cannula situated in the left ventricle and connected to a pump system outside the dog. This system enabled controlled increases or decreases of the end diastolic volume at any prechosen moment during the diastolic pause. Absolute volume variations in end diastolic volume and end systolic volumes could be calculated by combining the integrated flow signals from different consecutive beats. Left ventricular performance was evaluated in terms of end systolic volume and end systolic pressure variations. When the diastolic volume was abruptly increased by the pump system, natural mitral inflow decreased but end diastolic volume increased. The effect on diastolic pressure was dependent on the variation in filling rate, the amplitude of the infusion, the moment at which the infusion was started, and the diastolic pressure at the start of the infusion. Also stroke volume, maximal systolic pressure (Pmax), end systolic pressure, and end diastolic volume increased. The increased systolic performance was attributed to the increased end diastolic volume as expected according to Starling's law. When end diastolic volume was rapidly decreased during diastole by the pump, natural filling volumes increased to compensate for the volume loss by the pump. End diastolic volume was, however, smaller indicating that full compensation was not achieved. Evaluation of ventricular performance in terms of end systolic pressure and end systolic volume showed a decreased end systolic pressure and increased end systolic volume compared with the control values. The effect of a pump withdrawal was 1.62(0.38) times larger than could be explained on the basis of Starling's law. After the infusion of adrenaline the intrinsic depression disappeared and the influence of the volume withdrawal on cardiac performance was as expected from the Starling mechanism.

Direct recording of EDP-EDV relationship in isolated rat left ventricle: effect of diastolic crossbridge formation.

OBJECTIVE: The aim was to investigate whether the end diastolic pressure-end diastolic volume (EDP-EDV) relationship of the left ventricle can be influenced by calcium dependent elements, especially at low values of end diastolic pressure. METHODS: Isolated rat hearts were perfused in a modified Langendorff perfusion system. The EDP-EDV relationship of the left ventricle was investigated. Pressure was recorded with a microtip pressure catheter and volume with a microconductance catheter. Crossbridge cycling was affected by adding calcium antagonists (verapamil, diltiazem, nifedipine at 2.10(-7) M) or by adding the Mg-ATPase blocker BDM (2,3-butanedione-2-monoxime, 10(-3) M) to the perfusate. RESULTS: The above had a negative inotropic effect in systole. At EDP = 0 after stimulation the active isovolumetric pressure was zero. In diastole, BDM shifted the EDP-EDV relationship to slightly smaller EDVs. A decrease of about 5% in the EDV was found at lower EDP values. Ca2+ antagonists increased the EDV up to 40-80% at low EDP values. At higher EDP values only a small increase of EDV (about 10%) was found after verapamil perfusion. The results obtained are interpreted in terms of a three step crossbridge model. CONCLUSIONS: At low EDP, diastolic volume is dependent upon weakly bound crossbridges as a function of the [Ca2+] in the cardiac cell.

Cervical magnetic stimulation: the role of the neural foramen.

Magnetic stimulation of cervical nerve roots is a promising new technique, limited in part by uncertainty about the site of nerve depolarization. We used a modified "butterfly" stimulus coil with an easily defined excitation field to activate the C-8/T-1 nerve roots, recording over abductor digiti minimi. Locating both the lowest threshold for stimulation and the points of maximum stimulation, we determined the optimum rostral-caudal position and orientation for the stimulus coil over the posterior neck and upper trunk. The most favorable positions corresponded to the C-8/T-1 neural foramina, and the most favorable orientations to the roots within them. Additional measurements of depth and electric field suggested that the stimuli used should have been insufficient to activate nervous tissue in a homogeneous medium. A simple model indicates that the induced current is intensified where it passes through a bony foramen and explains preferential excitation of the nerve root at this site.

Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: a review.

Doxorubicin, a very potent and often used anti-cancer drug, has a wide spectrum of biological activity. Classic studies have demonstrated that doxorubicin and other members of the anthracycline family intercalate with DNA and partially uncoil the double-stranded helix. Doxorubicin has a high affinity for cell nuclei: as much as 60% of the total intracellular amount of doxorubicin is found in the nucleus. Once binding to DNA occurs, several consequences may ensue. The binding of anthracyclines to DNA inhibits DNA polymerase and nucleic acid synthesis. In addition, anthracyclines are known to stabilize the otherwise cleavable complex between DNA and homodimeric topoisomerase II enzyme subunits, resulting in the formation of protein-linked DNA double strand breaks. In tumor cells, these anthracycline-induced perturbations are believed to result in a final common pathway of endonucleolytic DNA fragmentation known as apoptosis. Because proliferation is an important determinant of tumor growth, interference with the genome is regarded as the primary cause of the anti-tumor action of doxorubicin. Intercalation with DNA may not be important in the cardiotoxicity associated with doxorubicin therapy (see next section), because cardiac cell proliferation in humans stops after 2 months of age. This review is focussed on the effects of doxorubicin on mechanical performance in skinned cardiac trabeculae after acute and chronic administration of doxorubicin. We look especially at the mechanical performance and the molecular changes observed and related to mechanical performance.

Doxorubicin interacts directly with skinned single skeletal muscle fibres.

The effect of doxorubicin, a highly effective anticancer agent, on the contractile apparatus of skinned single muscle fibres was tested in a concentration of 1 microM. Sarcomere length was set and held at 2 microns. Doxorubicin induced an increase in tension dependent on the Ca2+ concentration and time of incubation. The rise was up to 25% at [Ca2+] 40 microM. A parallel, small but significant shift of the calcium sensitivity curve, the relation between normalized tension and the negative logarithm of [Ca2+], the pCa, was observed. The results of this study suggest a direct interaction of doxorubicin with the actin myosin structure, possibly by an effect on myosin-ATP activity.

Ca2+ channel antagonists enhance tension in skinned skeletal and heart muscle fibres.

Striated muscle fibres, both skeletal and cardiac of different species including human, skinned by freeze-drying, were activated in solutions strongly buffered for Ca2+. The single fibres were immersed in solutions with different [Ca2+]. Sarcomere length was set and controlled by laser diffraction. Fibre type was determined by Sr2+ activation. The relation between the negative logarithm of the Ca2+ concentration and the normalized tension, the Ca2+ sensitivity curve, was investigated. The effect on the contractile machinery of three different Ca2+ channel antagonists (verapamil, diltiazem and nifedipine) in a therapeutic concentration (10(-6) M) was investigated. The possible effects on the Ca2+ sensitivity curve were quantified by: (1) the change in maximal tension developed at pCa2+ = 4.4; (2) the change in pCa2+ value at which 50% of the tension induced at pCa2+ = 4.4; (3) the steepness of the Ca2+ sensitivity curve in this point. The three drugs tested, at a therapeutic concentration of 1 microM, all enhanced maximal induced tension by respectively 25, 20 and 7%. The sarcomere length dependency of the effect proved to be dependent upon the drug, but also slightly on fibre type (skeletal or cardiac), or on species. It is concluded that the drug influences the cooperativity of the two different types of binding sites on troponin-C (low- and high-affinity sites). Tension enhancement was due to increased stiffness of the actin-myosin interaction site.

Dysphonia, an uncommon symptom of systemic neurotoxic envenomation by Vipera aspis bite. Report of two cases.

Two cases of Vipera aspis bites with severe envenomation in which, among other neurotoxic signs, dysphonia was observed, with alteration of the pitch of the voice are described. This uncommon symptom has never been reported in envenomation by European adders. It is pointed out that bites of European vipers should never be underestimated as severe envenomation may develop.

A case of intestinal infarction following Vipera aspis bite.

A case of Vipera aspis bite followed by severe envenomation, shock, neurotoxic symptoms, myoglobinuria and coagulation disorders with thrombosis of the iliac vessels and intestinal infarction is described. A right hemicolectomy had to be performed. Treatment is described in detail. European adder bites may cause, although uncommonly, severe envenoming with unusual symptoms. The attending doctor must be prepared to face unusual diagnostic and therapeutic problems.

Purification and characterisation of proteins with cardiac stimulatory and haemolytic activity from the anemone Actinia tenebrosa.

Three new proteins with cardiac stimulatory and haemolytic activity, designated tenebrosins-A, -B and -C, have been purified from the Australian sea anemone Actinia tenebrosa. These proteins are basic (pI greater than or equal to 9.4), have mol. wt of about 20,000, and have very similar amino acid compositions and N-terminal amino acid sequences. None of the proteins contains cysteine or cystine residues. On isolated, spontaneously beating guinea pig atria they exhibit at 1-2 nM strong positive inotropic and slight to moderate chronotropic effects. In some cases a transient negative inotropic effect occurs prior to onset of the positive inotropic response. The proteins are also haemolytic, producing 50% haemolysis of guinea pig erythrocytes at concentrations similar to those showing positive inotropic effects.

Direct action of estradiol-17 beta on the atrial action potential.

The effect of the two C-17 isomers of estradiol on the shape of the action potential of rat atrial tissue was studied by means of classical glass electrodes for different concentrations of estradiol. Resting potential and upstroke were not affected by estradiol, but the duration of the action potential was reduced. Only estradiol-17 beta exhibits an effect in a concentration dependent way, while estradiol-17 alpha has no effect at all. The ionic mechanism was studied by adding specific ionic blockers to the perfusate. Since the effect was much less pronounced when a slow inward current blocker was added, it was concluded that estradiol-17 beta acts mainly via the slow inward current channel. Only a small part of the interaction takes place via the potassium outward channel.

The effect of some sex hormones on the isovolumetric pressure curve of the rabbit's left ventricle.

The effect of some sex hormones (estradiol-17 alpha), estradiol-17 beta, estrone, progesterone and testosterone) on the mechanical activity of rabbit left ventricle was studied in concentrations within the physiological range. Investigations were carried out during the first ten minutes after the introduction of the steroid. Only progesterone and estradiol-17 beta affect the isovolumetric pressure curve; the other steroids do not exhibit any effect. The effects of estradiol-17 beta and progesterone counterbalance each other. Estradiol-17 beta enhances the rate of pressure development and decreases the time to reach peak pressure. Progesterone decreases both the rate of pressure development and the time to reach peak pressure.

The influence of velocity of length change on tension development in skeletal muscle: model calculations and experimental results.

Force responses obtained during constant velocity length changes on skeletal muscle tissue are simulated by means of two cross-bridge models proposed by Huxley and Simmons (1971, Nature 233, 533-538) and by Julian et al. (1974, Biophys. J. 14, 546-562). An implicit method was used for the numerical approximation in the simulations. The simulated force transients due to constant velocity length changes are found to be in qualitative agreement with re-investigated experimental results obtained from the whole sartorius muscle of the frog. A non-linear tension transient is observed, dependent both on amplitude and on velocity of release revealing an inflexion which gives the transient a shoulder shape. When velocity is increased the inflexion occurs earlier and at a lower tension value. A non-linear transient is observed during stretches performed at moderate velocities. Force responses are found to deviate concavely downwards from a linear time course. Simulations, however, predict a rather linear tension transient for comparable velocities. Implications of the experimental findings are discussed for both models.

High-speed transient-recording microprocessor system for the analysis of asymmetrical diffraction spectra from striated muscle.

A microprocessor based digital recording system has been developed to study the fine structure and asymmetry of diffraction spectra from striated muscle during contraction. Two linear 256-element photodiode arrays provide analog videosignals of the diffraction lines imaged onto these charged coupled devices. The photodiode arrays are alternately read and the videosignals can be digitized and stored within 1.36 ms (two images of 256 points) with a spatial resolution of 5 nm. (In this paper the spatial resolution is considered to be the standard deviation of the first-order maximum of a monochromatic wave of the He/Ne laser measured from the diode-arrays, using ideal gratings with a spacing between 1.6 and 3.6 microns.) The system's memory with a capacity of 192 pairs of images of 256 points can be optimized by means of a threshold to contain about 2000 images without any loss of information. A transient recording approach makes the system capable of recording long term slow phenomena of up to 5 s as well as fast events and the combination of fast events within slow processes. The system presented here has a significantly improved time resolution and storage capacity when compared to other systems and is more versatile. This is the first system which enables the simultaneous examination of the fine structure and asymmetry of diffraction spectra.

Influence of the culture medium on the synthesis of alpha-D-glucans by Streptococcus cricetus AHT.

Three different alpha-D-glucosyltransferases (GTFs) were separated from culture filtrates of Streptococcus cricetus strain AHT grown in a complex, standard medium in batch culture or under defined conditions of growth in the chemostat. Two of the enzymes (GTF-S1 and GTF-S2) converted sucrose into branched, soluble dextrans, and the third (GTF-I) produced a relatively linear, water-insoluble, predominantly (1----3)-linked alpha-D-glucan. When the organism was grown in complex medium modified by the removal of the fraction of high molecular weight, only GTF-S1 and GTF-S2 were released, and no GTF-I was detected. The water-insoluble glucan fraction obtained by incubating the cell-free filtrate with sucrose contained from 17 to 25% of (1----3)-glucosidic linkages, and accounted for up to 78 and 4% of the total glucans derived from growth in standard and modified medium, respectively. The soluble glucans produced in the same reaction were fractionated with ethanol to give, from both media, two distinct dextrans comprising (1) a highly branched dextran similar to the S1-dextran product of GTF-S1 and (2) a dextran containing fewer branch linkages and up to 86% of (1----6)-alpha-D-glucosidic linkages. A GTF responsible for the synthesis of the latter dextran was not separated. The structures of the glucan fractions and the products of the separated GTF were examined by enzymic degradation and methylation analysis.

Effects of dietary cholesterol and triglycerides on lipid concentrations in liver, plasma, and bile.

Dietary cholesterol (CHL) and triglycerides (TG) can influence plasma, hepatic, and biliary lipid composition, but effects on lipids in these three compartments during the early stages of CHL gallstone formation have not been studied in parallel. We fed prairie dogs diets containing one of four test oils (safflower, coconut, olive, or menhaden) at either 5 or 40% of calories, in the presence of 0 or 0.34% CHL, for 3 wk. In the absence of dietary CHL, increases in dietary TG produced 50-200% increases in the concentrations of biliary CHL and hepatic cholesteryl ester (CE), while the concentrations of hepatic free CHL (FC) as well as plasma FC and CE remained relatively unchanged. Increasing dietary CHL to 0.34% resulted in increases in hepatic FC of approximately 50% for all four fats regardless of whether they were supplied at 5 or 40% of calories. CHL supplementation caused more pronounced increases in biliary CHL (200-400%), hepatic CE (50-200%), plasma FC (up to 100%), and plasma CE (up to 150%), and these increases were exacerbated by concurrent supplementation of dietary fat and CHL (biliary CHL: 300-700%; hepatic CE: 100-250%; plasma FC: up to 165%; plasma CE: 100-350%). These results indicate that enhanced secretion of biliary CHL and, to a lesser extent, increased synthesis of hepatic CE, may be primary mechanisms for maintaining the hepatic FC pool. Furthermore, dietary CHL and high levels of fat intake are independent risk factors for increasing biliary CHL concentrations, and adverse effects on lipid concentrations in plasma and bile tend to be exacerbated by ingestion of diets rich in both fat and CHL.