bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching Student Nurses to be Culturally Safe: Can It Be Done?
Authors: Gibbs Kristy A.
Published: September 2005

From the perspective of a third-year student nurse about to graduate in New Zealand, this article discusses the complexities of teaching and learning the concept of cultural safety for educators and student nurses. The background of the implementation of cultural safety content into New Zealand nursing curriculum is briefly discussed, and the evolution of cultural safety and its diverse meanings that has led to some confusion among student nurses. How is cultural safety taught and what are the surrounding barriers? Also, where does the student nurse fit into this process? Recommendations are then made to improve the teaching of cultural safety in the New Zealand nursing curriculum.
Physicians’ Concerns About Home Health Care in Turkey: How Supportive Are They?
Authors: Kisa Adnan , Ersoy Korkut
Published: September 2005

Home health care is a low-cost alternative to traditional inpatient care and an appealing alternative for developing countries such as Turkey, where financial resources for health care are particularly scarce. To gain insight into the concerns of physicians regarding this possibility, a survey was administered to 200 physicians sampled at a large academic medical center in central Turkey. The results of the study indicate that 14% of the participants think that home health care in general is not appropriate for Turkey; however, 58% of participants felt that being close to one’s family when ill can have a significant effect on the course of the illness and recovery. The results of the study suggest that home health care is seen as an economically appealing but somewhat medically controversial area that nonetheless shows promise for future development in Turkey and other similarly developing countries.
D-glucuronyl C5-epimerase acts in dorso-ventral axis formation in zebrafish
Authors: Ghiselli Giancarlo , Farber Steven A
Published: September 2005

Background

Heparan sulfate (HS) is an ubiquitous component of the extracellular matrix that binds and modulates the activity of growth factors, cytokines and proteases. Animals with defective HS biosynthesis display major developmental abnormalities however the processes that are affected remain to be defined. D-glucuronyl-C5-epimerase (Glce) is a key HS chain modifying enzyme that catalyses the conversion of glucuronic acid into iduronic acid, a biosynthetic step that enhances HS biological activity. In this study the role of Glce during early zebrafish development has been investigated.

Results

Two Glce-like proteins (Glce-A and -B) are expressed in zebrafish at all times. They are the products of two distinct genes that, based on chromosomal mapping, are both orthologues of the same single human gene. Transcripts for both proteins were detected in fertilized zebrafish embryos prior to the onset of zygotic transcription indicating their maternal origin. At later developmental stages the epimerases are expressed widely throughout gastrulation and then become restricted to the hindbrain at 24 h post-fertilization. By monitoring the expression of well characterized marker genes during gastrulation, we have found that misexpression of Glce causes a dose-dependent expansion of the ventral structures, whereas protein knockdown using targeted antisense morpholino oligonucleotides promotes axis dorsalization. The ventralizing activity of Bmp2b is enhanced by Glce overexpression whereas Glce knockdown impairs Bmp2b activity.

Conclusion

Glce activity is an important determinant of of dorso-ventral axis formation and patterning in zebrafish. In particular Glce acts during gastrulation by affecting Bmp-mediated cell specification. The results obtained further corroborate the concept that HS encodes information that affect morphogenesis during early vertebrate development.
Functional genomics and expression analysis of the Corynebacterium glutamicum fpr2-cysIXHDNYZ gene cluster involved in assimilatory sulphate reduction
Authors: Rückert Christian , Koch Daniel J , Rey Daniel A , Albersmeier Andreas , Mormann Sascha , Pühler Alfred , Kalinowski Jörn
Published: September 2005

Background

Corynebacterium glutamicum is a high-GC Gram-positive soil bacterium of great biotechnological importance for the production of amino acids. To facilitate the rational design of sulphur amino acid-producing strains, the pathway for assimilatory sulphate reduction providing the necessary reduced sulfur moieties has to be known. Although this pathway has been well studied in Gram-negative bacteria like Escherichia coli and low-GC Gram-positives like Bacillus subtilis, little is known for the Actinomycetales and other high-GC Gram-positive bacteria.

Results

The genome sequence of C. glutamicum was searched for genes involved in the assimilatory reduction of inorganic sulphur compounds. A cluster of eight candidate genes could be identified by combining sequence similarity searches with a subsequent synteny analysis between C. glutamicum and the closely related C. efficiens. Using mutational analysis, seven of the eight candidate genes, namely cysZ, cysY, cysN, cysD, cysH, cysX, and cysI, were demonstrated to be involved in the reduction of inorganic sulphur compounds. For three of the up to now unknown genes possible functions could be proposed: CysZ is likely to be the sulphate permease, while CysX and CysY are possibly involved in electron transfer and cofactor biosynthesis, respectively. Finally, the candidate gene designated fpr2 influences sulphur utilisation only weakly and might be involved in electron transport for the reduction of sulphite. Real-time RT-PCR experiments revealed that cysIXHDNYZ form an operon and that transcription of the extended cluster fpr2 cysIXHDNYZ is strongly influenced by the availability of inorganic sulphur, as well as L-cysteine. Mapping of the fpr2 and cysIXHDNYZ promoters using RACE-PCR indicated that both promoters overlap with binding-sites of the transcriptional repressor McbR, suggesting an involvement of McbR in the observed regulation. Comparative genomics revealed that large parts of the extended cluster are conserved in 11 of 17 completely sequenced members of the Actinomycetales.

Conclusion

The set of C. glutamicum genes involved in assimilatory sulphate reduction was identified and four novel genes involved in this pathway were found. The high degree of conservation of this cluster among the Actinomycetales supports the hypothesis that a different metabolic pathway for the reduction of inorganic sulphur compounds than that known from the well-studied model organisms E. coli and B. subtilis is used by members of this order, providing the basis for further biochemical studies.
The neurotrophin receptor p75NTR mediates early anti-inflammatory effects of estrogen in the forebrain of young adult rats
Authors: Nordell Vanessa L , Lewis Danielle K , Bake Shameena , Sohrabji Farida
Published: September 2005

Background

Estrogen suppresses microglial activation and extravasation of circulating monocytes in young animals, supporting an anti-inflammatory role for this hormone. However, the mechanisms underlying estrogen's anti-inflammatory effects, especiallyin vivo, are not well understood. The present study tests the hypothesis that anti-inflammatory effects of estrogen are mediated by the pan-neurotrophin receptor p75NTR. Previously, we reported that estrogen attenuated local increases of interleukin(IL)-1β in the NMDA-lesioned olfactory bulb, while further increasing NGF expression.

Results

The present studies show that this lesion enhances expression of the neurotrophin receptor p75NTR at the lesion site, and p75NTR expression is further enhanced by estrogen treatment to lesioned animals. Specifically, estrogen stimulates p75NTR expression in cells of microvessels adjacent to the lesion site. To determine the role of this receptor in mediating estrogen's anti-inflammatory effects, a p75NTR neutralizing antibody was administered at the same time the lesion was created (by stereotaxic injections of NMDA) and specific markers of the inflammatory cascade were measured. Olfactory bulb injections of NMDA+vehicle (preimmune serum) increased IL-1β and activated the signaling molecule c-jun terminal kinase (JNK)-2 at 6 h. At 24 h, the lesion significantly increased matrix metalloproteinase (MMP)-9 and prostaglandin (PG)E2, a COX-2 mediated metabolite of arachadonic acid. All of these markers were significantly attenuated by estrogen in a time-dependent manner. However, estrogen's effects on all these markers were abolished in animals that received anti-p75NTR.

Conclusion

These data support the hypothesis that estrogen's anti-inflammatory effects may be, in part, mediated by this neurotrophin receptor. In view of the novel estrogen-dependent expression of p75NTR in cells associated with microvessels, these data also suggest that the blood brain barrier is a critical locus of estrogen's neuro-immune effects.
Causal inference based on counterfactuals
Authors: Höfler M
Published: September 2005

Background

The counterfactual or potential outcome model has become increasingly standard for causal inference in epidemiological and medical studies.

Discussion

This paper provides an overview on the counterfactual and related approaches. A variety of conceptual as well as practical issues when estimating causal effects are reviewed. These include causal interactions, imperfect experiments, adjustment for confounding, time-varying exposures, competing risks and the probability of causation. It is argued that the counterfactual model of causal effects captures the main aspects of causality in health sciences and relates to many statistical procedures.

Counterfactuals are the basis of causal inference in medicine and epidemiology. Nevertheless, the estimation of counterfactual differences pose several difficulties, primarily in observational studies. These problems, however, reflect fundamental barriers only when learning from observations, and this does not invalidate the counterfactual concept.
Anthracyclines, proteasome activity and multi-drug-resistance
Authors: Fekete Mirela R , McBride William H , Pajonk Frank
Published: September 2005

Background

P-glycoprotein is responsible for the ATP-dependent export of certain structurally unrelated compounds including many chemotherapeutic drugs. Amplification of P-glycoprotein activity can result in multi-drug resistance and is a common cause of chemotherapy treatment failure. Therefore, there is an ongoing search for inhibitors of P-glycoprotein. Observations that cyclosporin A, and certain other substances, inhibit both the proteasome and P-glycoprotein led us to investigate whether anthracyclines, well known substrates of P-gp, also inhibit the function of the proteasome.

Methods

Proteasome function was measured in cell lysates from ECV304 cells incubated with different doses of verapamil, doxorubicin, daunorubicin, idarubicin, epirubicin, topotecan, mitomycin C, and gemcitabine using a fluorogenic peptide assay. Proteasome function in living cells was monitored using ECV304 cells stably transfected with the gene for an ubiquitin/green fluorescent protein fusion protein. The ability of the proteasome inhibitor MG-132 to affect P-glycoprotein function was monitored by fluorescence due to accumulation of daunorubicin in P-glycoprotein overexpressing KB 8-5 cells.

Results

Verapamil, daunorubicin, doxorubicin, idarubicin, and epirubicin inhibited 26S chymotrypsin-like function in ECV304 extracts in a dose-dependent fashion. With the exception of daunorubicin, 20S proteasome function was also suppressed. The proteasome inhibitor MG-132 caused a dose-dependent accumulation of daunorubicin in KB 8-5 cells that overexpress P-glycoprotein, suggesting that it blocked P-glycoprotein function.

Conclusion

Our data indicate that anthracyclines inhibit the 26S proteasome as well as P-glycoprotein. Use of inhibitors of either pathway in cancer therapy should take this into consideration and perhaps use it to advantage, for example during chemosensitization by proteasome inhibitors.
The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia
Authors: Mortensen Eric M , Restrepo Marcos I , Anzueto Antonio , Pugh Jacqueline
Published: September 2005

Background

Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia.

Methods

A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation.

Results

Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22–0.89) was significantly associated with 30-day mortality.

Conclusion

Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.
Aggregation as bacterial inclusion bodies does not imply inactivation of enzymes and fluorescent proteins
Authors: García-Fruitós Elena , González-Montalbán Nuria , Morell Montse , Vera Andrea , Ferraz Rosa María , Arís Anna , Ventura Salvador , Villaverde Antonio
Published: September 2005

Background

Many enzymes of industrial interest are not in the market since they are bio-produced as bacterial inclusion bodies, believed to be biologically inert aggregates of insoluble protein.

Results

By using two structurally and functionally different model enzymes and two fluorescent proteins we show that physiological aggregation in bacteria might only result in a moderate loss of biological activity and that inclusion bodies can be used in reaction mixtures for efficient catalysis.

Conclusion

This observation offers promising possibilities for the exploration of inclusion bodies as catalysts for industrial purposes, without any previous protein-refolding step.
Sequence homology: A poor predictive value for profilins cross-reactivity
Authors: Sankian Mojtaba , Varasteh Abdolreza , Pazouki Nazanin , Mahmoudi Mahmoud
Published: September 2005

Background

Profilins are highly cross-reactive allergens which bind IgE antibodies of almost 20% of plant-allergic patients. This study is aimed at investigating cross-reactivity of melon profilin with other plant profilins and the role of the linear and conformational epitopes in human IgE cross-reactivity.

Methods

Seventeen patients with melon allergy were selected based on clinical history and a positive skin prick test to melon extract. Melon profilin has been cloned and expressed in E. coli. The IgE binding and cross-reactivity of the recombinant profilin were measured by ELISA and inhibition ELISA. The amino acid sequence of melon profilin was compared with other profilin sequences. A combination of chemical cleavage and immunoblotting techniques were used to define the role of conformational and linear epitopes in IgE binding. Comparative modeling was used to construct three-dimensional models of profilins and to assess theoretical impact of amino acid differences on conformational structure.

Results

Profilin was identified as a major IgE-binding component of melon. Alignment of amino acid sequences of melon profilin with other profilins showed the most identity with watermelon profilin. This melon profilin showed substantial cross-reactivity with the tomato, peach, grape and Cynodon dactylon (Bermuda grass) pollen profilins. Cantaloupe, watermelon, banana and Poa pratensis (Kentucky blue grass) displayed no notable inhibition. Our experiments also indicated human IgE only react with complete melon profilin. Immunoblotting analysis with rabbit polyclonal antibody shows the reaction of the antibody to the fragmented and complete melon profilin. Although, the well-known linear epitope of profilins were identical in melon and watermelon, comparison of three-dimensional models of watermelon and melon profilins indicated amino acid differences influence the electric potential and accessibility of the solvent-accessible surface of profilins that may markedly affect conformational epitopes.

Conclusion

Human IgE reactivity to melon profilin strongly depends on the highly conserved conformational structure, rather than a high degree of amino acid sequence identity or even linear epitopes identity.
Application of a disease-specific mapping function to estimate utility gains with effective treatment of schizophrenia
Authors: Lenert Leslie A , Rupnow Marcia FT , Elnitsky Christine
Published: September 2005

Background

Most tools for estimating utilities use clinical trial data from general health status models, such as the 36-Item Short-Form Health Survey (SF-36). A disease-specific model may be more appropriate. The objective of this study was to apply a disease-specific utility mapping function for schizophrenia to data from a large, 1-year, open-label study of long-acting risperidone and to compare its performance with an SF-36-based utility mapping function.

Methods

Patients with schizophrenia or schizoaffective disorder by DSM-IV criteria received 25, 50, or 75 mg long-acting risperidone every 2 weeks for 12 months. The Positive and Negative Syndrome Scale (PANSS) and SF-36 were used to assess efficacy and health-related quality of life. Movement disorder severity was measured using the Extrapyramidal Symptom Rating Scale (ESRS); data concerning other common adverse effects (orthostatic hypotension, weight gain) were collected. Transforms were applied to estimate utilities.

Results

A total of 474 patients completed the study. Long-acting risperidone treatment was associated with a utility gain of 0.051 using the disease-specific function. The estimated gain using an SF-36-based mapping function was smaller: 0.0285. Estimates of gains were only weakly correlated (r = 0.2). Because of differences in scaling and variance, the requisite sample size for a randomized trial to confirm observed effects is much smaller for the disease-specific mapping function (156 versus 672 total subjects).

Conclusion

Application of a disease-specific mapping function was feasible. Differences in scaling and precision suggest the clinically based mapping function has greater power than the SF-36-based measure to detect differences in utility.
The epidemiological impact of antiretroviral use predicted by mathematical models: a review
Authors: Baggaley Rebecca F , Ferguson Neil M , Garnett Geoff P
Published: September 2005

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.
Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug
Authors: Hardeland Rüdiger , Pandi-Perumal SR
Published: September 2005

Melatonin, originally discovered as a hormone of the pineal gland, is also produced in other organs and represents, additionally, a normal food constituent found in yeast and plant material, which can influence the level in the circulation. Compared to the pineal, the gastrointestinal tract contains several hundred times more melatonin, which can be released into the blood in response to food intake and stimuli by nutrients, especially tryptophan. Apart from its use as a commercial food additive, supraphysiological doses have been applied in medical trials and pure preparations are well tolerated by patients. Owing to its amphiphilicity, melatonin can enter any body fluid, cell or cell compartment. Its properties as an antioxidant agent are based on several, highly diverse effects. Apart from direct radical scavenging, it plays a role in upregulation of antioxidant and downregulation of prooxidant enzymes, and damage by free radicals can be reduced by its antiexcitatory actions, and presumably by contributions to appropriate internal circadian phasing, and by its improvement of mitochondrial metabolism, in terms of avoiding electron leakage and enhancing complex I and complex IV activities. Melatonin was shown to potentiate effects of other antioxidants, such as ascorbate and Trolox. Under physiological conditions, direct radical scavenging may only contribute to a minor extent to overall radical detoxification, although melatonin can eliminate several of them in scavenger cascades and potentiates the efficacy of antioxidant vitamins. Melatonin oxidation seems rather important for the production of other biologically active metabolites such as N
1-acetyl-N
2-formyl-5-methoxykynuramine (AFMK) and N
1-acetyl-5-methoxykynuramine (AMK), which have been shown to also dispose of protective properties. Thus, melatonin may be regarded as a prodrug, too. AMK interacts with reactive oxygen and nitrogen species, conveys protection to mitochondria, inhibits and downregulates cyclooxygenase 2.
Attitudes towards, and wishes for, euthanasia in advanced cancer patients at a palliative medicine unit
Authors: Johansen Sissel , Hølen Jacob Chr. , Kaasa Stein , Kaasa Stein , Loge Jon Håvard , Materstvedt Lars Johan
Published: September 2005

Background: Most studies on attitudes towards euthanasia and physician-assisted suicide (PAS) have been conducted in healthy populations. The aim of this study is to explore and describe attitudes towards, and wishes for, euthanasia/PAS in cancer patients with short life expectancy. Method: Semi-structured interviews with 18 cancer patients with a life expectancy of less than nine months. All patients were recruited from an inpatient palliative medicine unit. Results: Patients holding a positive attitude towards euthanasia/PAS do not necessarily want euthanasia/PAS for themselves. Wishes are different from requests for euthanasia/PAS. Fear of future pain and a painful death were the main reasons given for a possible wish for euthanasia/PAS. Worries about minimal quality of life and lack of hope also contributed to such thoughts. Wishes for euthanasia/PAS were hypothetical; they were future oriented and with a prerequisite that intense pain, lack of quality of life and/or hope had to be present. Additionally, wishes were fluctuating and ambivalent. Conclusion: The wish to die in these patients does not seem to be constant. Rather, this wish is more appropriately seen as an ambivalent and fluctuating mental ‘solution’ for the future. Health care providers should be aware of this when responding to utterances regarding euthanasia/PAS.
Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network
Authors: Klepstad Pa , Kaasa Stein , Cherny Nathan , Hanks Geoffrey , de Conno Franco ,   Research Steering Committee of the EAPC
Published: September 2005

The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids.

Patients were treated with analgesics corresponding to the WHO pain ladder step I (n / 855), step II (n / 509) and step III (n / 1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used nonopioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or coanalgesics used by / 1% of the patients were corticosteroids (39%), tricylic antidepressants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; iv or sc morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses.
The healthcare needs of chronic obstructive pulmonary disease patients in the last year of life
Authors: Elkington Helena , White Patrick , Addington-Hall Julia , Higgs Roger , Edmonds Polly
Published: September 2005

Chronic obstructive pulmonary disease (COPD) causes almost as many deaths as lung cancer, yet evidence about the impact of COPD in the latter stages of illness is limited. We assessed the healthcare needs of COPD patients in the last year of life through a retrospective survey of the informants of 399 deaths from COPD in four London health authorities between January and May 2001. We assessed symptoms, day to day functioning, contact with health and social services, formal and informal help with personal care, information received and place of death.

We obtained data on 209 (52%) deceased subjects (55% male), average age at death was 76.8 years. Based on the reports of informants of the deaths: 98% were breathless all the time or sometimes in the last year of life; other symptoms reported all the time or sometimes included fatigue or weakness (96%), low mood (77%) and pain (70%); breathlessness was partly relieved in over 50% of those treated; control of other symptoms was poor, with low mood relieved in 8% and no treatment for low mood received by 82% of sufferers; 41% left the house less than once a month or never; 47% were admitted to hospital at least twice in the last year of life; 51% received regular check-ups for their chest; 36% had check-ups by a hospital consultant; 35% saw their general practitioner (GP) less than once every three months or never; 63% knew they might die; 67% died in hospital. Patients who died from COPD lacked surveillance and received inadequate services from primary and secondary care in the year before they died. The absence of palliative care services highlights the need for research into appropriate models of care to address uncontrolled symptoms, information provision and end of life planning in COPD.
The House of Lords Select Committee on the Assisted Dying for the Terminally Ill Bill: implications for specialist palliative care
Authors: Finlay I G , Wheatley V J , Izdebski C
Published: September 2005

The Assisted Dying for the Terminally Ill Bill proposed to legalise both euthanasia and physician-assisted suicide for those with a terminal illness in the UK. A House of Lords Select Committee was convened to scrutinise this Bill and has recently published its report, which will be debated in Parliament on October 10th 2005.

The written and oral evidence submitted to the Select Committee represented a wide range of views on 'assisted dying'. Much of the evidence from those countries which have legalised euthanasia/physician-assisted suicide (The Netherlands, Belgium, Switzerland and Oregon, USA) dealt with the practicalities of ending life, and the legal procedures and safeguards instigated in these countries.

All the written and oral evidence in the public domain was scrutinised by the authors whilst the Select Committee was sitting. We have extracted those themes relevant to specialist palliative care practice and present them in this paper. We hope that this will provide a useful resource to inform the forthcoming public debate on assisted dying. The evidence of harms inherent in making such a change in the law, as presented to the Select Committee, has moved all three authors to oppose a change in the law.
Clinical Trial Results of a HER2/neu (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients
Authors: Peoples George E. , Gurney Jennifer M. , Hueman Matthew T. , Woll Mike M. , Ryan Gayle B. , Storrer Catherine E. , Fisher Christine , Shriver Craig D. , Ioannides Constantin G. , Ponniah Sathibalan
Published: September 2005

Purpose

E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC).

Patients and Methods

Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2+ patients (n = 24) were vaccinated, and HLA-A2− patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured.

Results

Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8+T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P < .01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2− patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P < .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response.

Conclusion

This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.
Prediction of Response to Neoadjuvant Chemotherapy by Sequential F-18-Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced-Stage Ovarian Cancer
Authors: Avril Norbert , Sassen Stefanie , Schmalfeldt Barbara , Naehrig Joerg , Rutke Stephan , Weber Wolfgang A. , Werner Martin , Graeff Henner , Schwaiger Markus , Kuhn Walther
Published: September 2005

Purpose

The aim of this study was to evaluate sequential F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) to predict patient outcome after the first and third cycle of neoadjuvant chemotherapy in advanced-stage (International Federation of Gynecology and Obstetrics stages IIIC and IV) ovarian cancer.

Patients and Methods

Thirty-three patients received three cycles of carboplatin-based chemotherapy, followed by cytoreductive surgery. Quantitative FDG-PET of the abdomen and pelvis was acquired before treatment and after the first and third cycle of chemotherapy. Changes in tumoral FDG uptake, expressed as standardized uptake values (SUV), were compared with clinical and histopathologic response; overall survival served as a reference.

Results

A significant correlation was observed between FDG-PET metabolic response after the first (P = .008) and third (P = .005) cycle of chemotherapy and overall survival. By using a threshold for decrease in SUV from baseline of 20% after the first cycle, median overall survival was 38.3 months in metabolic responders compared with 23.1 months in metabolic nonresponders. At a threshold of 55% decrease in SUV after the third cycle median overall survival was 38.9 months in metabolic responders compared with 19.7 months in nonresponders. There was no correlation between clinical response criteria (P = .7) or CA125 response criteria (P = .5) and overall survival. There was only a weak correlation (P = .09) between histopathologic response criteria and overall survival.

Conclusion

Sequential FDG-PET predicted patient outcome as early as after the first cycle of neoadjuvant chemotherapy and was more accurate than clinical or histopathologic response criteria including changes in tumor marker CA125. FDG-PET appears to be a promising tool for early prediction of response to chemotherapy.
American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer
Authors: Lyman Gary H. , Giuliano Armando E. , Somerfield Mark R. , Benson Al B. , Bodurka Diane C. , Burstein Harold J. , Cochran Alistair J. , Cody Hiram S. , Edge Stephen B. , Galper Sharon , Hayman James A. , Kim Theodore Y. , Perkins Cheryl L. , Podoloff Donald A. , Sivasubramaniam Visa Haran , Turner Roderick R. , Wahl Richard , Weaver Donald L. , Wolff Antonio C. , Winer Eric P.
Published: September 2005

Purpose

To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer.

Methods

An American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors.

Results

The literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes.

Conclusion

SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown.
Defining Cancer Patients As Being in the Terminal Phase: Who Receives a Formal Diagnosis, and What Are the Effects?
Authors: Aabom B. , Kragstrup J. , Vondeling H. , Bakketeig L.S. , Stovring H.
Published: September 2005

Purpose

Physicians either do not define cancer patients as being terminal, or their prognostic estimates tend to be optimistic. This might affect patients' appropriate and timely referral to specialist palliative care services or can lead to unintended acute hospitalization.

Patients and Methods

We used the Danish Cancer Register and four administrative registers to perform a retrospective cohort study in 3,445 patients who died as a result of cancer. We used the Danish “terminal declaration” issued by a physician as a proxy for a formal terminal diagnosis (prognosis of death within 6 months). The terminal declaration gives right to economic benefits and increased care for the dying. We investigated patient-related factors of receiving an explicit terminal diagnosis by logistic regression and then analyzed the effects of such a diagnosis on admission rate per week and place of death.

Results

Thirty-four percent of patients received a formal terminal diagnosis. Age of ≥ 70 years (odds ratio [OR], 0.44; 95% CI, 0.34 to 0.56; P < .001), women (OR, 0.81; 95% CI, 0.69 to 0.96; P = .02), hematologic cancer (OR, 0.20; 95% CI, 0.09 to 0.41; P < .001), and a less than 1-month survival time (OR, 0.10; 95% CI, 0.07 to 0.15; P < .001) were associated with a lesser likelihood of receiving a formal terminal diagnosis. Explicit terminal diagnosis was associated with lower admission rate and an adjusted OR of hospital death of 0.25 (95% CI, 0.21 to 0.29).

Conclusion

Women and the elderly were less likely to receive a formal terminal diagnosis. The formal terminal diagnosis reduced hospital admissions and increased the possibilities of dying at home.
The Value of Supplemental Prognostic Tests for the Preoperative Assessment of Idiopathic Normal-pressure Hydrocephalus
Authors: Marmarou Anthony , Bergsneider Marvin , Klinge Petra , Relkin Norman , Black Peter McL.
Published: September 2005

OBJECTIVE:

The diagnosis and management of idiopathic normal-pressure hydrocephalus (INPH) remains unclear. Moreover, the value of supplementary tests to predict which patients would benefit from placement of a shunt has not been established. This report develops evidence-based guidelines for the use of supplementary tests as an aid in prognosis.

METHODS:

MEDLINE searches from 1966 to the present were undertaken by use of the query NPH, normal-pressure hydrocephalus, lumbar drain, CSF [cerebrospinal fluid] tap test, and external CSF drainage in humans. This resulted in 242 articles. To provide a scientific, evidence-based review, we have chosen to restrict our analysis to clinically relevant studies usually consisting of large numbers of shunted NPH patients. Studies that did not specify INPH or secondary NPH were considered in a separate evidentiary table.

RESULTS:

Evidence-based guidelines for use in supplementary tests have been developed. A positive response to a 40- to 50-ml tap test has a higher degree of certainty for a favorable response to shunt placement than can be obtained by clinical examination. However, the tap test cannot be used as an exclusionary test because of its low sensitivity (26–61%). Determination of the CSF outflow resistance via an infusion test carries a higher sensitivity (57–100%) compared with the tap test and a similar positive predictive value of 75 to 92%. Prolonged external lumbar drainage in excess of 300 ml is associated with high sensitivity (50–100%) and high positive predictive value (80–100%).

CONCLUSION:

To date, a single standard for the prognostic evaluation of INPH patients is lacking. However, supplemental tests can increase predictive accuracy for prognosis to greater than 90%. Additional multicenter prospective randomized clinical trials are needed.
Paradoxical Cerebral Herniation Secondary to Lumbar Puncture after Decompressive Craniectomy for a Large Space-occupying Hemispheric Stroke: Case Report
Authors: Oyelese Adetokunbo A. , Steinberg Gary K. , Huhn Stephen L. , Wijman Christine A.C.
Published: September 2005

OBJECTIVE AND IMPORTANCE:

The risk of transtentorial herniation after removal of cerebrospinal fluid from the lumbar cistern in the setting of a supratentorial lesion with significant mass effect, increased cerebrospinal fluid pressure, or midline shift is well known. We report a case of cerebral herniation from intracranial hypotension (so-called paradoxical herniation) secondary to a lumbar puncture 1 month after decompressive hemicraniectomy for a large right hemispheric stroke.

CLINICAL PRESENTATION:

A 50-year-old woman was transferred to our neurosurgical service for obtundation 4 days after a lumbar puncture to rule out meningitis and 1 month after decompressive craniectomy for a large right hemispheric stroke.

INTERVENTION:

Eighty grams of mannitol was administered before transfer. On arrival at our hospital, the patient was intubated and a computed tomographic scan was performed. The patient was diagnosed with low-pressure herniation after review of the computed tomographic scan. Rehydration was initiated, and the patient was placed in the Trendelenburg position. She became easier to arouse, but her pupils remained dilated. She experienced a sudden severe cardiac arrhythmia leading to a cardiac arrest. Attempted resuscitation was unsuccessful, and the patient was pronounced dead.

CONCLUSION:

Lumbar punctures may result in lethal intracranial hypotension in patients after hemicraniectomy and are thus contraindicated unless care is taken to remove the pressure gradient of atmospheric air across the lumbar cistern.
External Rotation as a Result of Suprascapular Nerve Neurotization in Obstetric Brachial Plexus Lesions
Authors: Pondaag Willem , de Boer Ralph , van Wijlen-Hempel Marie S. , Hofstede-Buitenhuis Sonja M. , Malessy Martijn J.A.
Published: September 2005

OBJECTIVE:

Obstetric brachial plexus lesions may cause lifelong limitations of upper limb function. Nerve repair is widely advocated in infants who do not show spontaneous recovery. Typically, the suprascapular nerve (SSN) is involved in the lesion. Neurotization of the SSN routinely is performed, aiming at reinnervation of the infraspinatus muscle to restore external rotation. The results after SSN neurotization have not, as yet, been studied in detail; therefore, this study was undertaken. Of special interest was the comparison of two commonly applied SSN neurotization procedures: nerve grafting from C5 versus nerve transfer of the accessory nerve.

METHODS:

Infants with obstetric brachial plexus lesions after nerve grafting of C5 to the SSN (n = 65) or nerve transfer of the accessory nerve to the SSN (n = 21) were selected for retrospective analysis after a mean follow-up period of 3 years. Outcome was expressed in degrees of true glenohumeral external rotation. This was defined as the angle between the position of the 90 degrees (actively or passively) flexed elbow resting against the abdomen and the position of the flexed elbow after external rotation with the upper arm held in adduction by the investigator. This movement can be executed only by infraspinatus muscle contraction. In addition, functional external rotation was evaluated by testing the ability to reach the mouth and the back of the head.

RESULTS:

Only 17 (20%) of the 86 patients reached more than 20 degrees of external rotation, whereas 35 (41%) were unable to perform true external rotation. There was no statistically significant difference between nerve grafting from C5 and extraplexal nerve transfer using the accessory nerve. Functional scores showed that 88% can reach the mouth and that 75% can reach the head.

CONCLUSION:

The restoration of a fair range of true glenohumeral external rotation after neurotization of the SSN in infants with obstetric brachial plexus lesions, whether by grafting from C5 or by nerve transfer of the accessory nerve, is disappointingly low. However, it seems that compensatory techniques contribute to effectuate a considerable range of movement.
Cost-effectiveness of Intraoperative Imaging in Carotid Endarterectomy
Authors: Burnett Mark G. , Stein Sherman C. , Sonnad Seema S. , Zager Eric L.
Published: September 2005

OBJECTIVE:

There has never been a large, randomized controlled trial to assess the impact of intraoperative imaging on the success of carotid endarterectomy (CEA). This comparison involves cost-effectiveness analysis.

METHODS:

We constructed a decision-analytic model to compare effectiveness and costs of intraoperative ultrasound (IUS) and completion angiography as adjuncts to CEA. Data on procedural mortality, morbidity, and costs were obtained from the English-language literature. The review included a total of 52 reports, encompassing more than 22,000 patients. The main components of costs were those of the monitoring interventions and the care of perioperative stroke.

RESULTS:

Mean perioperative outcome without completion imaging is approximately 96.7% of what it would be in the absence of perioperative stroke or death. IUS and completion angiography each result in approximately 2% improvement in expected outcome. Mean perioperative costs are $396.50 for IUS, $721.30 for no monitoring, and $840.90 for completion angiography. Because IUS is significantly more effective at detecting technical errors that would likely result in perioperative stroke than no imaging and is significantly less costly than angiography, this strategy dominates the other two (i.e., it provides greater effectiveness at lower cost).

CONCLUSION:

Although surgical complications are uncommon, IUS substantially lowers the rate of perioperative stroke and mortality and thus is significantly more cost-effective than either completion angiography or no operative imaging.
Tumoral Calcinosis of the Filum Terminale
Authors: Sharma M , Sinha R , Hussey K , Fouyas I P.
Published: September 2005

OBJECTIVE AND IMPORTANCE:

Tumoral calcinosis is a rare disorder presenting with tumor-like masses of calcification, usually in soft tissues around large joints. Although this condition has been reported in the spine, this is the first reported instance of this uncommon lesion occurring in the intradural compartment, involving the filum terminale.

CLINICAL PRESENTATION:

A 55-year-old man presented with back and right leg pain. Initial investigations revealed no cause. A review of his original magnetic resonance imaging scans revealed an intradural calcified mass at L3 level. Surgical exploration was undertaken.

INTERVENTION:

A L3 laminectomy revealed a calcified mass adherent to the filum terminale. Frozen section from this mass revealed tumoral calcinosis involving the filum terminale.

CONCLUSION:

This is the first known case of intradural involvement by tumoral calcinosis. This is an uncommon disorder, and a high index of suspicion is required to diagnose the condition, which can recur if incompletely removed.