Palliation und Frakturprävention

Sind Skelettmetastasen nachweisbar, so ist dies ein untrügliches Zeichen dafür, dass sich die Tumorerkrankung im gesamten Organismus ausgebreitet hat. Eine Heilung ist nur in seltenen F?llen zu erwarten. Die Therapie ist in diesem Stadium eher palliativ. Bei konservativer Therapiestrategie sollte wegen des Risikos von pathologischen Frakturen eine Abstimmung mit dem Chirurgen und Orthop?den erfolgen, um ggf. rechtzeitig operativ zu intervenieren. W?hrend eine pr?ventive operative Stabilisierung im Bereich der langen R?hrenknochen relativ unproblematisch ist, kann sie im Becken- und Wirbels?ulenbereich Komplikationen mit sich bringen.     

Clinical facilitators: a new way of working

AIM: To improve the quality and quantity of student clinical placements in an NHS trust. METHOD: When nurse training was under review, a 12-month pilot study was undertaken to introduce 12 clinical facilitators to acute and surgical wards at six trust sites on a supernumerary basis. As well as guiding the student, each facilitator liaised with a link tutor and ward staff, thereby maintaining continuity. The project team worked closely with the trust audit department and collected data using a variety of methods. The project leader developed an audit questionnaire for students, ward staff and college tutors. The initial answers were used as a baseline, then the same questionnaire was redistributed so the data could be analysed and compared. RESULTS: Most of the students felt more supported and confident to practise. The clinical facilitators were able to help ground the tutors' practice knowledge in reality, and the tutors built up the clinical facilitators' confidence in curricular issues and skills, such as presentation and teaching strategies. CONCLUSION: The clinical facilitator can strengthen partnerships between education and service and offer a model for practical facilitation.     

Early spatial memory deficit induced by 2,5-hexanedione in the rat

2,5-Hexanedione (2,5-HD), the major common neurotoxic metabolite of n-hexane and methyl n-butyl ketone, causes a delayed neuropathy with associated sensorimotor impairments. The question arises as to whether specific cognitive deficits occur even prior to changes in sensorimotor ability. The present experiments examined the effects of 2,5-HD on spatial navigation of rats in a water maze at levels/times that did not affect spontaneous exploratory motor activity in an open field holeboard apparatus. Exposure to 1% 2,5-HD in the drinking water for 2 weeks did not significantly affect escape learning, as measured by latency to find a hidden platform. However, 2,5-HD treated animals were impaired in the use of a spatial strategy during a recall test. A similar impairment in spatial memory was observed after i.p. injection of 500 mg/kg/day 2,5-HD for 4 days, in the absence of significant changes in sensorimotor ability or weight loss. Thus 2,5-HD may mediate some of the cognitive effects of hexacarbons and these changes can occur prior to the development of motor symptoms.     

Inhibition of furin-like enzymes blocks interleukin-1alpha/oncostatin M-stimulated cartilage degradation

OBJECTIVE: To investigate the role of furin-like enzymes in the proteolytic cascades leading to cartilage breakdown and to examine which collagenase(s) contribute to collagen degradation. METHODS: Bovine nasal cartilage was stimulated to resorb with the addition of interleukin-1alpha (IL-1alpha)/oncostatin M (OSM) in the presence or absence of a furin inhibitor, Dec-RVKR-CH(2)Cl, or selective matrix metalloproteinase 1 (MMP-1) inhibitors. Collagen and proteoglycan levels were determined by assay of hydroxyproline and sulfated glycosaminoglycan, respectively. Collagenase and gelatinase activity were measured using (3)H-acetylated collagen and gelatin zymography, respectively. RESULTS: The addition of Dec-RVKR-CH(2)Cl to stimulated cartilage reduced the release of collagen fragments and the levels of active collagenase and MMP-2, suggesting that furin-like enzymes are involved in the cascades leading to activation of procollagenases. At MMP inhibitor concentrations that selectively inhibit MMP-1, no inhibition of collagen release was observed, but increasing the concentration to the 50% inhibition concentration for MMP-13 resulted in a 50% blockage of collagen release. The addition of Dec-RVKR-CH(2)Cl to resorbing cartilage also partially blocked proteoglycan release, thus demonstrating a role for furin-activated enzymes in the pathways leading to proteoglycan degradation. CONCLUSION: Furin-like enzymes are involved in cascades leading to activation of procollagenases and degradation of collagen. MMP-13, which can be activated by furin-processed membrane-type 1 MMP-1, appears to be a major collagenase involved in collagen degradation induced by IL-1alpha/OSM. Furin-like enzymes also appear to play a role in the pathways leading to proteoglycan degradation. These findings are of importance when considering proteinase inhibition as a target for therapeutic intervention in arthritic diseases.     

Case Reports. Chronic and acute Aspergillus meningitis

Cerebral aspergillosis usually occurs in severely immunocompromized hosts, is difficult to diagnose, and has a poor prognosis. After 14 months of chronic meningitis, ventriculitis, choroid plexitis, and lumbar arachnoiditis, which was complicated by acute hydrocephalus, Aspergillus, suspected to be from the candidus group, was isolated from the cerebrospinal fluid (CSF) of a previously healthy man. Thereafter Aspergillus antigen was found in stored plasma and CSF samples. He was treated with voriconazole and itraconazole. In a haemodialysis patient affected by an acute meningococcal meningitis, following a 3-day symptom-free interval, symptoms and signs of acute meningitis had reappeared and were unresponsive to a broad antimicrobial coverage. However, they resolved within 5 days after liposomal amphotericin B treatment had been started. From his CSF Aspergillus-DNA was identified and Aspergillus fumigatus isolated by culture. These two different clinical cases show that Aspergillus-DNA and antigen detection tests represent an advance in the diagnosis and liposomal amphotericin B, voriconazole, and itraconazole are an advance in the treatment of Aspergillus meningitis.     

Using GI-specific patient outcome measures in renal transplant patients: Validation of the GSRS and GIQLI

Introduction: Gastrointestinal (GI) side-effects occur frequently as a result of immunosuppressant regimens used in renal transplant patients. Little effort has been made to quantify the impact of these side-effects on patients’ health-related quality of life and symptom severity. Objective: To assess the psychometric characteristics of two GI-specific outcome instruments (the Gastrointestinal Rating Scale (GSRS) and the Gastrointestinal Quality of Life Index (GIQLI)) for use in post-renal transplant patients. Methods: Cross-sectional study conducted at 5 clinical centers in 4 countries. Patients were required to be on mycophenolate mofetil and a calcineurin inhibitor. Patients completed the GSRS, GIQLI and two generic instruments (the Psychological General Well-Being Index and the EQ-5D) at one timepoint. Reliability, construct and known groups validity were assessed. Results: In general the GSRS and the GIQLI demonstrated Cronbach’s alphas higher than 0.70. The GIQLI was moderately to highly correlated with the PGWB and EQ-5D. Correlations among the GSRS and generic instruments were slightly lower. The GSRS and GIQLI both distinguished between patients with and without GI complaints (all p<0.05). Conclusions: The GSRS and the GIQLI are appropriate for use in a post-renal transplant population. Scores on both instruments demonstrated significant differences between renal transplant patients with GI complications and without GI complications.     

A randomized, controlled trial of high-dose dextromethorphan in facial neuralgias

BACKGROUND: NMDA glutamate receptor antagonists such as ketamine and dextromethorphan reduce pain in certain neuropathic pain conditions. However, there have been no controlled trials of NMDA antagonists in facial neuralgias. METHODS: A randomized, double-blind, crossover trial compared 6 weeks of oral dextromethorphan with active placebo (low-dose lorazepam) in 19 patients, stratified into three groups: 11 with facial pain and possible trigeminal neuropathy, five with anesthesia dolorosa, and three with idiopathic trigeminal neuralgia. Dosage was titrated in each patient to the highest level reached without disrupting normal activities. RESULTS: Patients completing the trial included 10 with possible trigeminal neuropathy, four with anesthesia dolorosa, and two with trigeminal neuralgia. In patients with possible trigeminal neuropathy and anesthesia dolorosa, dextromethorphan decreased pain by a mean of only 2 to 4%, and these estimates were not significant. Both patients with trigeminal neuralgia had more pain during dextromethorphan treatment than during placebo treatment. Of three patients who demonstrated an analgesic response to dextromethorphan during the main trial, only one repeatedly responded in four subsequent confirmatory drug-placebo crossovers. CONCLUSIONS: Dextromethorphan shows little or no analgesic efficacy in pain due to possible trigeminal neuropathy and anesthesia dolorosa. Additional trials are necessary to conclusively evaluate the efficacy of NMDA-receptor antagonists in trigeminal neuralgia.     

Validation of the PowerRefractor for measuring human infant refraction.

PURPOSE: Eccentric photorefraction provides an opportunity to gather rapid and remote estimates of refraction and gaze position from infants. The technique has the potential for extensive use in vision screenings and studies of visual development. The goal of this study was to assess the refraction calibration of the PowerRefractor (Multichannel Systems) for use with uncyclopleged infants. METHODS: The defocus measurements from the instrument were compared with the results of simultaneous retinoscopy in one analysis and with known amounts of defocus induced with trial lenses in another. Data were collected from infants 1 to 6 months of age and adults. RESULTS: The PowerRefractor typically read < 1 D of myopia when the retinoscopy reflex was judged to be neutral at the same working distance in both infants and adults. The slopes of both infant and adult validation functions (trial lens power vs. measurement of induced defocus) were close to 1 over a 4D range. The infant slopes were significantly greater than those of the adults, however. CONCLUSIONS: The results suggest that the instrument is capable of detecting large amounts of defocus but needs individual calibration for detailed studies of accommodative accuracy and absolute levels of defocus, as has been recommended previously for adult subjects.     

Weight loss in breast cancer patient management.

PURPOSE: To systematically review and summarize evidence relevant to obesity and breast cancer clinical outcome, potential hormonal mediating mechanisms, and the current status of weight loss interventions for chronic disease management. METHODS: A comprehensive, formal literature review was conducted to identify 5,687 citations with key information from 159 references summarized in text and tables. This process included a search for all breast cancer studies exploring associations among survival or recurrence and obesity at diagnosis or weight gain after diagnosis using prospective criteria. RESULTS: On the basis of observational studies, women with breast cancer who are overweight or gain weight after diagnosis are found to be at greater risk for breast cancer recurrence and death compared with lighter women. Obesity is also associated with hormonal profiles likely to stimulate breast cancer growth. Recently, use of weight loss algorithms proven successful in other clinical settings that incorporate dietary therapy, physical activity, and ongoing behavior therapy have been endorsed by the National Institutes of Health and other health agencies. CONCLUSION: Although definitive weight loss intervention trials in breast cancer patients remain to be conducted, the current evidence relating increased body weight to adverse breast cancer outcome and the documented favorable effects of weight loss on clinical outcome in other comorbid conditions support consideration of programs for weight loss in breast cancer patients. Recommendations for the clinical care of overweight or obese breast cancer patients are offered.     

American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for women with hormone receptor-positive breast cancer: status report 2002.

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTIONS: Anastrozole, letrozole, and exemestane. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO)-prescribed technology assessment procedure was followed. BENEFITS/HARMS: The ASCO panel recognizes that a woman and her physician's decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non-cancer-related risks and benefits. CONCLUSION: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002). A 5-year course of adjuvant tamoxifen remains the standard therapy for women with hormone receptor-positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the panel are summarized in Appendix 3.) VALIDATION: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.