Ex vivo reversal of chemoresistance by tariquidar (XR9576)

The expression of P-glycoprotein (P-gp) has been demonstrated to confer resistance to several anticancer drugs, including anthracyclines, taxanes and vinca alkaloids. Tariquidar is a novel inhibitor of P-gp that has been shown to reverse resistance to cytotoxic drugs in tumor cell lines and mouse xenografts. We have used an ATP-based chemosensitivity assay (ATP-TCA) to compare the activity of cytotoxic drugs in combination with tariquidar against a variety of solid tumors (n = 37). The expression of P-gp was determined in a subset of solid tumor samples by immunohistochemistry (n = 16). Resistance was seen in 20 of 37 (54%) tumors tested with doxorubicin, in 27 of 34 (79%) samples tested with paclitaxel and 17 of 31 (55%) with vinorelbine. Tariquidar alone showed no activity over a wide range of concentrations up to 2 microM (n = 14). The median IC90s for doxorubicin, paclitaxel and vinorelbine, alone were 2.57, 27.4 and 15.5 microM. These decreased to 1.67 (p<0.0005), 20.6 (p<0.05) and 9.5 microM (p<0.001), respectively, in combination with tariquidar. Tariquidar also significantly decreased resistance in 14 of 20 (70%), six of 27 (22%) and six of 17 (35%) samples tested with doxorubicin, paclitaxel and vinorelbine, respectively. Immunohistochemical staining for P-gp was positive in nine of 16 (56%) samples and in all of these cases addition of tariquidar improved the activity of the cytotoxic. The results show that tariquidar is able to decrease resistance in a number of solid tumors resistant to cytotoxic drugs known to be P-gp substrates. These data support the introduction of tariquidar in combination with chemotherapy to clinical trials of patients expressing P-gp.     

Delirium and psychotic symptoms--an integrative model

Delirium may be a common cause of psychotic symptoms such as hallucinations, bizarre delusions and thought-disorder, even in conditions such as schizophrenia, mania and depression, where delirium has traditionally been excluded by definition. This situation is a consequence of the insensitivity of current clinical criteria for the diagnosis of delirium, which recognize only the most severe forms of functional brain impairment (including disorientation and clouding of consciousness). Serial electroencephalograms (EEGs) are the most sensitive method for detecting delirium, and until such studies are performed, the true incidence of delirium in psychotic patients will not be known. The suggested causal mechanism of delirium in psychosis is sleep disruption. Sleep is essential for maintenance of memory circuits, which otherwise suffer progressive synaptic weakening due to molecular turnover. When sleep is disrupted, memory circuits deteriorate, and subsequent activation of incompetent circuits can generate psychotic symptoms. Induction of physiologically normal sleep would therefore be expected to produce significant clinical improvement in patients with psychotic symptoms. Furthermore, the 'anti-delirium' action of electroconvulsive therapy may account for its effectiveness in alleviating a wide range of psychiatric and neurological pathologies.     

A path model of factors influencing the academic performance of nursing students

AIMS: The aim of this study was to build and test a model describing some of the psychological processes underlying nursing students' academic performance. The model hypothesized that age and entry qualifications influence students' academic motivation (locus of control, academic worries, self-efficacy, and expectations), and that this in turn affects their decisions to seek support, which subsequently influences their academic performance. RATIONALE AND BACKGROUND: A literature search showed that previous academic motivation research is piecemeal. The present work sought to integrate previous findings into a coherent framework as a way of advancing our understanding of the complex interactive nature of the factors influencing student performance. METHOD: Path analysis was performed on data obtained from questionnaires and university records for 315 students undertaking a preregistration diploma course in nursing at a university in the Northwest of England. RESULTS: Support-seeking was more predictive of student performance than entry qualifications. Support-seeking also mediated the age-performance relationship: greater willingness to seek support led to the better academic performance of older students. Other features of the accepted model suggested that students who judged their self-efficacy to be higher expected higher grades and that these highly optimistic expectations led to less support-seeking. Academic worries and internal control beliefs were also found to have positive influences on support-seeking. The model developed accounted for 24% of the variance in students' academic performance. DISCUSSION: Implications for nurse education, and interventions that focus on improving students' academic motivation are discussed in the context of the 'personal teacher' support framework.     

The European Smoking Prevention Framework Approach (EFSA): an example of integral prevention

A smoking prevention project in six European countries (European Smoking prevention Framework Approach) was developed, featuring activities for adolescents, schools and parents, including out-of-school activities. Consensus meetings resulted in agreement between the countries on goals, objectives and theoretical methods. Countries' specific objectives were also included. National diversities required country-specific methods to realize the goals and objectives. The community intervention trial was used as the research design. Since interventions took place at the community level, communities or regions were allocated at random to the experimental or control conditions. Complete randomization was achieved in four countries. At baseline, smoking prevalence among 23 125 adolescents at the start of the project was 5.6% for regular smoking and 4.0% for daily smoking. Smoking prevalence rates were higher among girls than boys in all countries as far as weekly smoking was concerned. Process evaluations revealed that the project's ambitions were high, but were limited by various constraints including time and delays in receiving funds. Future smoking prevention projects should aim to identify the effective components within the social influence approach as well as within broader approaches and on reaching sustained effects.     

Clinical outcome of anterior cruciate ligament reconstruction with quadrupled hamstring tendon graft and bioabsorbable interference screw fixation

BACKGROUND: To date, there has been no publication of clinical follow-up data on patients who have undergone quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable screw fixation. PURPOSE: To report the results of quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation. STUDY DESIGN: Retrospective review. METHODS: Sixty-five patients (66 knees) were retrospectively identified by chart review as having undergone quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation with a minimum 2-year follow-up. RESULTS: Data were collected on 48 knees in 47 patients (73%) at an average 30.2 months (range, 24 to 43) after surgery. Thirty-six patients (37 knees) returned for clinical evaluation (56% return) and subjective follow-up only was obtained in 11 patients (17%). The mean Lysolm knee score was 91 (range, 45 to 98), with a mean of 97 for the uninvolved knee. The mean Tegner activity score was 5.7 (range, 3 to 7). The KT-1000 arthrometer mean side-to-side difference for manual maximum displacement was 2.03 mm (range, -1 to 8). The mean International Knee Documentation Committee knee score was 83 (range, 47 to 100). Patients who underwent associated partial meniscectomy or meniscal repair had significantly lower International Knee Documentation Committee scores than patients without associated procedures (P < 0.01). CONCLUSIONS: Quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation is comparable with other methods of anterior cruciate ligament reconstruction in terms of patient satisfaction, knee stability, and function.     

Vaginal adenosis with adenocarcinoma in situ in a woman with no recognised antecedent factors

We present a case of vaginal adenosis with adenocarcinoma in situ in a woman with no recognised antecedent factors. This case demonstrates the importance of continuing thorough colposcopic assessment of the entire lower genital tract with repeated biopsies of all abnormal epithelium in women with persistent or recurrent cervical cytology abnormalities. Successful management requires accurate definition of the vaginal lesion.     

Stylohyoid syndrome: a case report

Elongation of the styloid process and/or ossification of the stylohyoid ligament can be associated with cervical pharyngeal pain, which may be detected both clinically and radiographically. Eagle's syndrome, stylohyoid syndrome, and pseudostylohyoid syndrome should be considered in the differential diagnosis.