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.

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.

[Historical observations on shoulder dystocia. 1) From the origin to Jacquemier]. / Considerazioni storiche sulla distocia delle spalle. 1)-Dalle origini a Jacquemier.

The result of a literature survey on shoulder dystocia from year 1609 to 1860 are presented. Operative maneuvers for the resolution of dystocia were mainly examined, as well as the development of knowledge about the pathogenetic mechanism of this serious complication.

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.

NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats.

Although substance P (SP) has been implicated as a mediator of neurogenic inflammation in the small intestine, little information is available regarding the role of SP in the pathogenesis of chronic ulcerative colitis. In this study, our aim was to investigate whether the intraperitoneal administration of a nonpeptide neurokinin-1 (NK-1) antagonist, CP-96345, which antagonizes the binding of SP to its NK-1 receptor, results in the attenuation of colonic inflammation induced in rats by 5% dextran sodium sulfate (DSS) in drinking water for 10 days compared with an inactive enantiomer, CP-96344. Disease activity was assessed daily for 10 days, after which colonic tissue damage was scored and myeloperoxidase activity and colon and urinary 8-isoprostanes were measured. Animals receiving DSS exhibited marked physical signs of colitis by day 5 compared with controls. Chronic administration of the NK-1 antagonist significantly reduced the disease activity index, mucosal myeloperoxidase activity, colonic tissue damage score, and mucosal and urinary levels of 8-isoprostanes compared with inactive enantiomer- or vehicle-injected (saline) animals receiving DSS alone. These data indicate that the administration of an NK-1 antagonist can attenuate colonic inflammation and oxidative stress and suggest a novel therapeutic approach in the treatment of chronic ulcerative colitis.

The length dependency of calcium activated contractions in the femoral artery smooth muscle studied with different methods of skinning.

The relationship between the calcium concentration and the isometric tension obtained with different techniques of skinning provides information on the biochemical events of contraction in vascular smooth muscle. Muscle preparations of the rabbit femoral artery were skinned with triton X-100, saponin, beta-escin and alpha-toxin and the relationship between the calcium concentration and isometric tension was determined at different preparation lengths. We determined the calcium sensitivity as a function of muscle length with different techniques of skinning. At a pCa of 6.0, triton X-100 skinned smooth muscle of the femoral artery generated 50% of the maximal tension. In alpha-toxin skinned preparations, this calcium sensitivity was shifted to a pCa of 5.6. The sensitivity of the saponin and 3-escin skinned preparations were in between those of the triton X-100 and the alpha-toxin skinned preparations. The cooperativity of the regulation of contraction varied among the differently skinned preparations between 3 (alpha-toxin) and 6 (triton X-100). The relationships between the calcium concentration and the isometric tension of the differently skinned preparations up to the optimal length for tension generation did not exhibit any length dependency. The length tension relationship, obtained from the maximal response at the highest calcium concentration is in line with that from other studies. The presence of intracellular proteins and membranes affects the regulation of contraction in smooth muscle of the femoral artery.

Doxorubicin impairs crossbridge turnover kinetics in skinned cardiac trabeculae after acute and chronic treatment.

Crossbridge dynamics underlying the acute and chronic inotropic effects of doxorubicin (Dox) were studied by application of releasing length steps (amplitude, 0.5-10%) to skinned cardiac trabeculae. Acute incubation of trabeculae with 20 microM Dox for 30 min resulted in a decrease of the velocity of unloaded shortening (V(0), from 9.3 +/- 1.1 to 7.7 +/- 0.7 microm/s, P <.05) and in an increase of the rate of force redevelopment (tau(r), from 56 +/- 4 to 65 +/- 3 ms, P <.05) in response to step amplitudes ranging from 5 to 10%. In contrast, chronic Dox treatment in rats (2 mg/kg/week for 4 weeks) significantly impaired trabecular crossbridge dynamics after step releases of 0.5%. This was reflected by an increase of all time constants describing tension recovery: tau(1), from 10 +/- 1 to 14 +/- 1 ms; tau(2), from 65 +/- 6 to 82 +/- 6 ms; tau(3), from 92 +/- 7 to 293 +/- 67 ms; P <.05. In addition, V(0) was decreased (from 8.6 +/- 0.6 to 6.8 +/- 0.3 microm/s, P <.05) and tau(r) was increased (from 67 +/- 4 to 89 +/- 3 ms; P <.05) in the slack-test. We found that chronic Dox treatment resulted in a shift from the "high ATPase" alpha-myosin heavy chain (MHC) isoform toward the "low-ATPase" beta-MHC isoform in the ventricles (control: alpha-MHC 79 +/- 2% and beta-MHC 21 +/- 2%; Dox-treated: alpha-MHC 53 +/- 2% and beta-MHC 47 +/- 2%; P <.05). The present results show that acute Dox incubation affects the detachment rate of crossbridges, which leads to a delayed relaxation and an arrest of crossbridges in strongly bound states. In contrast, chronic Dox treatment leads to an impairment of both the attachment and detachment rates in the crossbridge cycle, which may be explained by an altered MHC isoform composition in ventricular myocardium. Interfering with Dox-induced alterations of crossbridge kinetics may provide a new strategy to prevent Dox-associated cardiotoxicity.

Role of stasis and oxidative stress in ileal pouch inflammation.

BACKGROUND: Although ileal pouch-anal anastomosis has become the operation of choice for patients with chronic ulcerative colitis and familial adenomatous polyposis coli, ileal pouch inflammation or pouchitis remains a significant postoperative complication. Numerous factors such as fecal stasis have been implicated in the etiology of pouchitis; however, pouchitis remains poorly understood due to the lack of a small animal model. One of the primary goals of this study was to surgically create a reservoir or U-pouch in the ileum of a rat in which stasis would occur in a manner that was unimpeded by other complicating factors such as a colectomy. This model would allow investigation of the hypothesis that intestinal stasis leads to biochemical changes that predispose the ileal pouch to inflammation and oxidative stress. MATERIALS AND METHODS: A U-pouch was surgically created in the terminal ileum of Lewis rats just proximal to the ileocecal valve without a colectomy. Stasis was assessed by serial barium radiographs over 48 h. Thirty days after surgery, mucosa was obtained from the ileal U-pouches and nonoperated ileum to assess inflammation and neutrophil infiltration histologically and by measuring myeloperoxidase activity. Oxidative stress was assessed by measuring 8-isoprostane levels in urine. Once the model was validated and it was established that stasis and inflammation occurred in the pouch, either vitamin E or allopurinol was administered for 30 days after which myeloperoxidase and 8-isoprostane levels were again measured. RESULTS: In our experimental model, ileal stasis resulted in increases in both mucosal myeloperoxidase activity and urinary 8-isoprostane levels, suggesting that oxidative stress was associated with stasis. Thirty-day treatment with vitamin E or allopurinol reduced ileal myeloperoxidase activity and urinary 8-isoprostane levels. CONCLUSION: These studies demonstrated that stasis in the ileum occurred and was associated with neutrophil infiltration and oxidative stress. Antioxidant treatment reduced the inflammatory response suggesting a role for antioxidant therapy in the treatment of pouchitis.

Electrophoretic Deposition: A Quantitative Model for Particle Deposition and Binder Formation from Alcohol-Based Suspensions.

We investigated electrophoretic deposition from a suspension containing positively charged particles, isopropanol, water, and Mg(NO(3))(2), with the aim of describing the deposition rates of the particles and Mg(OH)(2), which is formed due to chemical reactions at the electrode, in terms of quantitative models. LaB(6) particles were used as a model system. The particle layer is consolidated by simultaneous precipitation of Mg(OH)(2) which acts as a binder to hold the particles together. The Mg(OH)(2) content was determined solely by the amount of charge passed through the cell. Quantitative precipitation of all OH(-) formed at the electrode was observed, except at very low current. The occurrence of a minimum current was ascribed to a threshold for Mg(OH)(2) deposition. The same minimum current was observed for particle deposition. In combination with results using NaNO(3), where no adherent layer was formed, this illustrates that Mg(OH)(2) binder is necessary for consolidation. Once the minimum current was exceeded, it was found that all particles that migrate to the electrode under the influence of the electric field contribute to the formation of the layer, i.e., the "sticking coefficient" for the particles equals 1.0. The applicability of the particle and Mg(OH)(2) deposition models was tested by variation of the Mg(NO(3))(2) concentration, pH, and water content. Copyright 2000 Academic Press.

A preliminary evaluation of a sheep blowfly trap in the Western Cape.

An insecticide-free sheep blowfly trapping system, utilising a synthetic lure, was evaluated at 4 localities in the Western Cape. Control sites, where no suppression was practised, were identified for each locality. The blowfly population was monitored for 48 hours monthly at each of the localities. Five to 7 suppression traps at the respective localities were identified for this purpose. Three to 10 traps were set monthly for monitoring in the control areas. Trapping resulted in the suppression (P < 0.01) of the Lucilia population at Caledon, where a large area of approximately 50 km2 was trapped. The suppression area of all the localities was < or =850 ha. At Elsenburg, blowfly numbers were low. There was a strong suggestion of a general reduction in the Lucilia numbers at this locality. Trapping failed to reduce Lucilia numbers at Tygerhoek and Langgewens. Lack of control over the influx of Lucilia from adjacent sheep-producing areas probably contributed to this result. The observed response at Elsenburg was probably due to its situation in a predominantly wine-growing area. Most of the blowflies recovered from the control traps during the month with the highest yield at the respective localities belonged to the genus Lucilia. The results obtained at Caledon and published reports suggest that large-scale trapping of Lucilia spp. may play a role in an integrated pest management system for blowflies.

The effect of length on the sensitivity to phenylephrine and calcium in intact and skinned vascular smooth muscle.

The length dependency of the sensitivity to activators of the smooth muscle of different blood vessels is not yet fully understood. Muscle preparations of the aorta, the femoral artery and the portal vein of the rabbit were investigated for the length dependency of the sensitivity to phenylephrine and calcium in both intact and triton X-100 skinned preparations. For intact smooth muscles we found that at increased preparation length, the sensitivity of contraction was increased. The femoral artery showed the largest effect and the portal vein the smallest. In the skinned preparations of the three preparations the calcium sensitivity was not dependent on the preparation length. We conclude that the changes of the sensitivity in intact preparations are not caused by changes of the calcium sensitivity of the contractile proteins.

Force generation and shift of mass between myosin and actin in skinned striated muscle fibres at low calcium concentrations.

Skinned muscle fibres from the gracilis muscle of the rabbit were used to record small angle X-ray diffraction spectra under various contractile conditions. The intracellular calcium concentration, expressed as pCa, was varied between 8.0 and 5.74. Equatorial diffraction spectra were fitted by a function consisting of five Gaussian curves and a hyperbola to separate the (1.0), (1.1), (2.0), (2.1) and Z-line diffraction peaks. The hyperbola was used to correct for residual scattering in the preparation. The ratio between the intensities of the (1.1) and (1.0) peaks was defined as the relative transfer of mass between myosin and actin, due to crossbridge formation after activation by calcium. The relation between the ratio and the relative force of the fibre (normalized to the force at pCa 5.74 and sarcomere length 2.0 microns) was linear. At high pCa (from pCa 6.34 to 8.0) no active force was observed, while the ratio still decreased. Sarcomere length was recorded by laser diffraction. The laser diffraction patterns did not show changes in sarcomere length due to activation in the high pCa range (between 8.0 and 6.34). From these results the conclusion is drawn that crossbridge movement occurs even at subthreshold calcium concentrations in the cell, when no active force is exerted. Since no force is generated this movement may be related to crossbridges in the weakly bound state.

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.

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.

Accreditation of prior learning: is it worth it? An evaluation of a pilot scheme.

Accreditation of Prior Learning (APL) is a relatively new process for both students and colleges of nursing and claims to offer many benefits (Open University 1990, Fox et al 1992). This paper describes the findings of a study undertaken to determine students' experiences of the APL process and their perceptions of how the APL process developed them. A sample of 14 students reported on the use of APL to obtain academic credit for a Level I Welsh National Board Framework Module. The results indicated both some difficulties and benefits associated with using the APL process. The majority of students experienced difficulty in reflecting on prior learning and practice. This seemed to be due in part to the students' reluctance to value their clinical learning experiences. Many of the sample also reported difficulty in maintaining motivation over the period of time allocated to complete the APL process. All the students undertook the process in their own time and had to submit the module summative assignment in addition to the APL evidence required. These factors may have further influenced motivational levels. Clear positive outcomes were that APL was felt to be a worthwhile process, even increasing self-esteem for some individuals. It also enabled students to develop reflective writing skills and to value clinical experience. Recommendations were made to both facilitate and enhance the APL experience for future students, and to promote critical reflection within the nursing profession as a whole.

The effect of actin filament compliance on the interpretation of the elastic properties of skeletal muscle fibres.

Recently, X-ray diffraction studies provided direct evidence for an appreciable length change in the actin filament upon activation. This finding has profound implications on the interpretation of the elastic properties of skeletal muscle fibre. In this study we determined the compliance of the actin filament during activation, using the data obtained previously from quick stretch and release experiments on skeletal muscle fibres of the frog. The effects of filament compliance are demonstrated clearly in the elastic properties of partially activated fibres. The low-frequency elasticity increases linearly with tension, reflecting an increase in the number of force-producing cross-bridges. At higher frequencies, this linearity is lost. In this study we describe the data consistently in terms of a cross-bridge stiffness increasing linearly with tension and a constant Young's modulus for the actin filament of 44 MN m-2. This corresponds to a compliance of 23 pm microns-1 per kN m-2 tension developed. Using this value for the actin filament Young's modulus, its contribution to the elastic properties of skeletal muscle fibre of the frog is considered in rigor and relaxation. The filament compliance hardly affects the overall elasticity of the muscle fibre in relaxation. In contrast, it contributes to a large extent to the overall elasticity in rigor. Taking account of the filament compliance, we find that the Young's modulus in rigor exhibits an increase from 14 MN m-2 at frequencies below 500 Hz to 55 MN m-2 above 40 kHz.