bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological factors associated with use of home nebulized therapy for COPD
Authors: Bosley CM , Corden ZM , Rees PJ , Cochrane GM
Published: April 2003

This study examined the relationship between adherence to domiciliary nebulized therapy and psychological factors; patient attitudes, anxiety, depression, and quality of life. Ninety three patients aged 45-77 yrs with chronic obstructive pulmonary disease (COPD) and using domiciliary nebulizers were recruited from a hospital database. They completed the St George's respiratory questionnaire (SGRQ)-1 and the hospital anxiety and depression scale (HADS) and attended a semistructured interview. Their usual nebulizers were replaced by Dataloggers, which record the date, time and duration of each treatment, to use for 4 weeks. The SGRQ was then repeated (SGRQ-2). Eighty two patients completed the study. Fifty six percent were poorly adherent; taking less than 70% of the dose prescribed (or less than 60% on regimens of > or = 5 times daily). The total scores on the SGRQ-2 were negatively correlated with percentage adherence. Multiple regression analysis showed that the SGRQ-2 total score was associated with percentage adherence, depression score, feeling supported by clinic staff, and patients feeling that they tried to ignore their chest disease. Patients who report poor quality of life are more likely to be depressed, feel unsupported by clinic staff and be poorly adherent to treatment. Increased levels of clinic support, with the addition of psychological treatments, may be of benefit to some patients with chronic obstructive pulmonary disease.
Comparison of a limited computerized diagnostic system (ResCare Autoset) with polysomnography in the diagnosis of obstructive sleep apnoea syndrome
Authors: Kiely JL , Delahunty C , Matthews S , McNicholas WT
Published: April 2003

The increasing numbers of patients referred for evaluation of suspected obstructive sleep apnoea (OSA) places a growing burden on available sleep laboratory resources. A number of limited diagnostic systems have been developed in an effort to cope with this clinical problem. In this study, the diagnostic capabilities of one limited diagnostic system (ResCare Autoset) were compared with full polysomnography (PSG), using the Oxford SAC computerized system. Thirty six patients with suspected OSA had simultaneous studies performed both with the Autoset and Oxford PSG systems. The apnoea plus hypopnoea index (AHI) (events x h(-1)) scored by the Autoset system was compared with the AHI scored from the PSG raw tracings by an experienced sleep technician. There were highly significant correlations between the Autoset AHI and the AHI scored by the manual PSG scoring method (r=0.92; p<0.001). The positive predictive value for diagnosis of OSA for the Autoset was 86% when compared with manual PSG scoring, based on an AHI threshold for OSA of 15 events x h(-1). However, the agreement between Autoset and PSG was poor in severe cases of OSA, although not sufficiently so as to result in mistaken diagnosis in any of these cases. We conclude that the Autoset system is a sensitive and easy to use system, which facilitates screening for obstructive sleep apnoea with a reasonable degree of accuracy.
Respiratory muscles and weaning failure
Authors: Vassilakopoulos T , Zakynthinos S , Roussos Ch
Published: April 2003

Weaning failure is, unfortunately, a rather common phenomenon for mechanically-ventilated patients (especially those with chronic obstructive pulmonary disease (COPD)), and the respiratory muscles play a pivotal role in its development. Weaning fails whenever an imbalance exists between the ventilatory needs and the neurocardiorespiratory capacity. This can happen if there is an increase in the energy demands of the respiratory muscles, a decrease in the energy available, a decrease in neuromuscular competence, or if the respiratory muscles pose an impediment to the heart and blood flow. The imbalance created will lead to weaning failure through the development of respiratory muscle fatigue, hypercapnia, dyspnoea, anxiety and organ dysfunction.
Medical management of primary pulmonary hypertension
Authors: Kneussl MP , Lang IM , Brenot FP
Published: April 2003

Primary pulmonary hypertension (PPH) is a poorly understood, progressive disease that is characterized by elevation of pulmonary artery pressure and vascular resistance, leading to right ventricular failure and death within 2-3 yrs after diagnosis. Based upon the concept that vasoconstriction and thrombotic occlusion of resistance vessels precipitate this process, vasodilator therapy and anticoagulation have become the main strategies for improving survival in these patients. Whereas, a few years ago, medical therapy of primary pulmonary hypertension was perceived as a bridging therapy to lung or heart lung transplantation, modes of therapy are being clinically tested at this time to offer an alternative to the surgical treatment of this disease. However, no selective pulmonary vasodilator is yet available. Therefore, and because of the potential hazards of vasodilator treatment, standardized haemodynamic testing is performed prior to initiation of vasodilator treatment. In this update, the currently available compounds both for haemodynamic testing and chronic therapy, their mode of action, method of administration and efficacy are reviewed.
BAL fluid LDH activity and LDH isoenzyme pattern in lipoid pneumonia caused by an intravenous injection of lamp oil
Authors: Drent M , Cobben NA , Henderson RF , Jacobs JA , Wouters EF , van Dieijen-Visser MP
Published: April 2003

A 30 year old man developed lipoid pneumonia after an injection of lamp oil. In addition to "foamy" alveolar macrophages, bronchoalveolar lavage (BAL) fluid analysis showed an increased number of neutrophils. Moreover, lactate dehydrogenase (LDH) and alkaline phosphatase activities were elevated. The increase seen in LDH activity both in serum and BAL fluid was accompanied by shifts in the isoenzyme pattern in similar directions for both fluids. These findings suggest a pulmonary source for the temporary serum as well as BAL fluid LDH increase. This case indicates the usefulness of bronchoalveolar lavage fluid analysis as a probe to detect pulmonary injury caused by a pneumotoxicant and, probably, to monitor recovery or deterioration.
Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects
Authors: Evangelopoulos M E , Alevizaki M , Toumanidis S , Sotou D , Evangelopoulos C D , Koutras D A , Stamatelopoulos S F , Mavrikakis M
Published: April 2003

Mitral valve prolapse (MVP) has been reported to be associated with systemic lupus erythematosus (SLE). The aim of the present study was to determine the prevalence of MVP in SLE patients, assess its clinical significance and examine the possible association of this entity with other autoimmune indices. Eighty-seven consecutive SLE patients attending the rheumatology clinic and 73 normal control subjects were examined by M-mode, two-dimensional color-Doppler echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. MVP was detected in 19=87 patients with SLE and in four of the healthy controls (P = 0.0057). SLE patients with MVP were younger (33.6±12.4 years) than those without MVP (41.1±12.9, P = 0.04) and with shorter duration of the disease (P = 0.03). We found a statistically higher prevalence of anticardiolipin antibodies (aCL) in SLE patients with prolapse (11=19) compared with SLE patients without prolapse (15=68, P = 0.04). This association was independent of age. The aCL-IgG levels were significantly higher in SLE patients with MVP (32.37±43.26) compared with SLE patients without MVP (22.24±29.95, P = 0.04). Thyroid autoantibodies tended to be more common in SLE patients with MVP. The prevalence of MVP is increased in SLE patients. The presence of aCL and of organ-specific autoantibodiesin SLE patients with MVP might indicate the autoimmune origin of MVP. The possibility that SLE patients with MVP may be predisposed to further autoimmune diseases should be considered.
Quinacrine added to ongoing therapeutic regimens attenuates anticardiolipin antibody production in SLE
Authors: Toubi E , Kessel A , Rosner I , Rozenbaum M , Lorber M , Paran D , Sabo E , Golan T D
Published: April 2003

The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5 - 12), the addition of Qn (100 mg=day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6 - 10. Prior to Qn treatment the therapeutic regimens of 12 months’ duration, included in all cases HCQ (400 mg=day), in many cases prednisone (P, 10 - 20 mg=day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15 - 18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8 - 12 months of follow-up (P = 0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P = 0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent’s effect is permanent needs further elucidation.
Systemic lupus erythematosus-associated pulmonary hypertension: good outcome following sildenafil therapy
Authors: Molina J , Lucero E , Luluaga S , Bellomio V , Spindler A , Berman A
Published: April 2003

A 46-year-old woman with systemic lupus erythematosus(SLE) and concomitant severe pulmonary hypertension (PH) is described. Other secondary causes of PH including thromboembolism, phospholipid syndrome, valvular disease and interstitial pulmonary involvement were ruled out. Owing to her lack of clinical response to conventional therapy, sildenafil was begun at increasing doses up to 400 mg daily. Both clinical and hemodynamic improvement ensued. This appears to be the first clinical report of the use of sildenafil in SLE followed by resolution of severe PH.
Ruptured renal microaneurysms complicated with a retroperitoneal abscess for a patient with systemic lupus erythematosus
Authors: Tsai Y-G , Lai J-H , Kuo S-Y , Chen H-C , Wan H-L , Chang D-M
Published: April 2003

Renal artery aneurysm is extremely rare among patients with systemic lupus erythematosus.(SLE). Herein, we report on a 22-year-old male lupus patient who presented with acute abdominal pain, anemia and subsequent hypertension. Abdominal computed tomography revealed a peri-renal hematoma over the right kidney. A renal angiography revealed bilateral renal microaneurysms. The patient subsequently developed a right-side retroperitoneal abscess 4 weeks after hematoma formation and received an emergent laparotomy with drainage. Subsequent culture of the abscess-derived fluid revealed the presence of Proteus mirabilis and Escherichia coli. Following appropriate antipyretic and immunosuppressive drugs therapy, the patient recovered successfully. To the best of our knowledge, this is the first report of SLE associated with a retro-peritoneal abscess probably secondary to a ruptured renal microaneurysm.
Mycobacterium avium complex-associated hemophagocytic syndrome in systemic lupus erythematosus patient: report of one case
Authors: Yang W-K , Fu L-S , Lan J-L , Shen G-H , Chou G , Tseng C-F , Chi C-S
Published: April 2003

Hemophagocytic syndrome (HPS) in systemic lupus erythematosus(SLE) patients has not commonly been reported. In this case study, we report the first case of Mycobacterium avium complex (MAC)-associated hemophagocytic syndrome in a patient with systemic lupus erythematosus (SLE). This SLE patient, a 15-year-old girl, had been on a high dose of prednisolone (> 0.5 mg=kg=day) for more than 3 years. She presented with a spiking fever, hepatosplenomegaly, pancytopenia, hyperferritinemia and adult respiratory distress syndrome. Bone marrow examination revealed hemophagocytosis as well as non-caseating granulomatosis. There was no indication of SLE flare-up. She responded poorly to initial treatment with methyl-prednisolone, intravenous immunoglobulin, etoposide, and drugs for Mycobacterium tuberculosis including rifampin, ethambutol, isoniazid and pyramide. However, gastric lavage culture revealed MAC. Following treatment with clarithromycin, ciprofloxacin and amikacin, her condition gradually improved and she was discharged 3 months after admission. In SLE patients with pancytopenia and hyperferritinemia, MAC-associated HPS should be considered in the differential diagnosis.
Chronic monoarthritis of the knee in systemic lupus erythematosus
Authors: Wong R CC , Kong K O , Lin R VTP , Barkham T
Published: April 2003

We describe a middle-aged lady with systemic lupus erythematosus who presented with chronic left knee monoarthritis without constitutional symptoms. The histology of synovial tissue taken at arthroscopy showed acute inflammation and Erysipelothrix rhusiopathiae, identified with some difficulty, was isolated from the enrichment broth only. Blood cultures were negative. Her history revealed significant exposure to pond fish. She responded well to intravenous penicillin and remains well 12 months later.
Systemic lupus erythematosus in three ethnic groups: XV prevalence and correlates of fibromyalgia
Authors: Friedman A W , Tew M B , Ahn C , McGwin G , Fessler B J , Bastian H M , Baethge B A , Reveille J D , Alarcón G S ,   LUMINA Study Group
Published: April 2003

The purpose of this study was to determine the prevalence and correlates of fibromyalgia (FM) in a prospective, multiethnic systemic lupus (SLE) cohort. A total of 266 SLE patients with disease duration of ≤5 years at study entry were evaluated longitudinallyfor the presence of FM (per ACR criteria). Sociodemographicfactors, behavioral=psychologicalvariables, clinical features, serologic factors (autoantibodies), and self-reportedfunctioning(MOS SF-36) were ascertainedin all patients. Subjects were evaluated at study entry and annually thereafter. The prevalence of FM was then calculated, as was the prevalence of FM-like manifestations (widespread pain with at least 6, but fewer than 11=18 tender points). Variables were evaluated for association with FM or FM-like manifestationsby univariate and stepwise logistic regressionanalyses.FM was present in 14 patients (5%; 9=92 Caucasians (C), 4=109 African Americans (AA), 1=65 Hispanics (H)) and FM=FM-like manifestationsin 35 (13%; 16 C, 9 AA, 10 H). There was no difference noted between those with and without FM with respect to gender, education level, income below poverty level, disease activity or damage. By stepwise logistic regression analyses, the strongest association with both FM and FM=FM-like manifestationswas a self-reported history of anxiety or affective disorder (P = 0.0237, OR = 4.6 and P = 0.0068, OR = 3.4, respectively). Caucasian ethnicity was strongly associated with FM (P = 0.0066, OR = 7.5) and African American ethnicity was negatively associated with FM=FM-like (P = 0.0204, OR = 0.3). Poorer self-reported physical functioning was associated with FM=FM-like (P = 0.0443, OR = 0.96). FM and FM-like manifestations correlate best with the presence of Caucasian ethnicity, concomitant anxiety or affective disorder, and to a lesser extent with poorer self-reported physical functioning. African American ethnicity is negatively associated with the combination of FM and FM-like manifestations. Clinical measures of disease activity, disease damage, specific organ dysfunction, sociodemographicfactors and serologic features are not correlated with FM in this early SLE cohort.
Use of a new fluorescence immunoassay to detect anti-dsDNA antibodies is more correlated with disease activity and complement than the ELISA method in SLE patients
Authors: Chen C-Y , Tseng H-M , Chen L-C , Tsao C-H , Kuo M-L , Ou L-S , Huang J-L
Published: April 2003

To determine whether the serum levels of anti-double strand DNA (anti-dsDNA) autoantibodies detected using a newly developed fluorescence immunoassay (FIA) in patients with systemic lupus erythematosus (SLE) correlated more with clinical parameters, such as SLE disease activity index (SLEDAI), complement and the occurrence of nephritis when compared with traditional enzyme-linked immunosorbent assay (ELISA), we prospectively collected 124 serum samples from 31 patients who had juvenile-onset SLE and were regularly monitored every 2 months at our outpatient clinic. At every visit, clinical manifestations and laboratory parameters were assessed and the SLEDAI was determined. Correlation analyses between the two different measurements of anti-dsDNA antibodies and SLEDAI, serum complement levels and the occurrence of nephritis were performed. The results showed that anti-dsDNA autoantibodies detected using both ELISA and FIA significantly correlated with SLEDAI, and significantly and inversely correlated with the serum levels of C3 and C4. FIA had significantly higher correlation with SLEDAI and C4 than did ELISA. The mean values of anti-dsDNA antibodies detected using FIA in patients with nephritis were significantly higher than in those without nephritis. In contrast, the values of anti-dsDNA antibodies detected using ELISA did not show significant differences between these two groups. We conclude that FIA had better correlationwith SLEDAI, C4 and the occurrenceof nephritis, and comparable correlationswith C3 that were similar to the results found using ELISA. Thus, it is worthwhile developing the FIA method for clinical evaluation of disease activity in SLE patients.
Validation of a systemic lupus activity questionnaire (SLAQ) for population studies
Authors: Karlson E W , Daltroy L H , Rivest C , Ramsey-Goldman R , Wright E A , Partridge A J , Liang M H , Fortin P R
Published: April 2003

The goal of this work was to develop an economical way of tracking disease activity for large groups of systemic lupus erythematosus (SLE) patients in clinical studies. A Systemic Lupus Activity Questionnaire (SLAQ) was developed to screen for possible disease activity using items from the Systemic Lupus Activity Measure (SLAM) and tested for its measurement properties. The SLAQ was completed by 93 SLE patients just prior to a scheduled visit. At the visit, a rheumatologist, blinded to SLAQ results, examined the subject and completed a SLAM. Associations among SLAQ, and SLAM (omitting laboratory items) and between individual items from each instrument were assessed with Pearson correlations. Correlations between pairs of instruments were compared using Student’s t-tests. The mean score across all 24 SLAQ items was 11.5 (range 0 -33); mean SLAM without labs was 3.0 (range 0 -13). The SLAQ had a moderately high correlation with SLAM-nolab (r = 0.62, P < 0.0001). Correlations between patient-clinician matched pairs of items ranged from r = 0.06 to 0.71. Positive predictive values for the SLAQ ranged from 56 to 89% for detecting clinically significant disease activity. In studies of SLE, symptoms suggesting disease can be screened by self-report using the SLAQ and then verified by further evaluation.
Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients
Authors: Soltész P , Veres K , Lakos G , Kiss E , Muszbek L , Szegedi G
Published: April 2003

We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects with lupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, b2glycoprotein I (b2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.
Predictors of poor renal outcome in patients with lupus nephritis treated with combined pulses of cyclophosphamide and methylprednisolone
Authors: Cortés-Herández J , Ordi-Ros J , Labrador M , Segarra A , Tovar J L , Balada E , Vilardell-Tarres M
Published: April 2003

Lupus nephritis remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Although the renal prognosis has improved, the optimal therapeutic regime has not been definitively established, and significant challenges remain in the management of disease progression and recurrent renal relapse. We performed a prospective study to evaluate the outcome of 38 patients with severe lupus nephritis treated with standard cyclophosphamide and methylprednisolone pulse therapy, and to determine the variables associated with poor outcome. Five patients developed end-stage renal disease (ESRD) (13%), 10 (26%) developed persistent proteinuria (>1 g=24 h) and 15 (39%) suffered at least one relapse after 8 years of follow-up. A high chronicity index, interstitial fibrosis (P = 0.04), persistent hypertension (P < 0.0001) and hypocomplementaemia(P = 0.002) after treatment were the major variables associated with ESRD. Tubular atrophy (P = 0.01), persistent hypertension (P = 0.0001) and hypocomplementaemia after treatment (P = 0.0281) were associated with persistent proteinuria. Persistence of anti-dsDNA antibodies and hypocomplementaemia after treatment (P = 0.0118) were associated with renal relapse.

Our data suggest that the group of patients with persistence of hypocomplementaemiaand raised anti-dsDNA antibodies titres are at high risk of renal relapse and may be candidatesfor continuation of immunosuppressive treatment. Patients with persistent proteinuria alone or a high chronicity index are less likely to respond to immunosuppression, and strict control of the hypertension may be the best approach.
Association of the TAP2*Bky2 allele with presence of SS-A/Ro and other autoantibodies in Japanese patients with systemic lupus erythematosus
Authors: Kanagawa S , Morinobu A , Koshiba M , Kageyama G , Hayashi N , Yoshino S , Tokano Y , Hashimoto H , Kumagai S
Published: April 2003

We previously reported that a new allele of transporter associated with antigen processing (TAP) 2 gene, TAP2*Bky2 (Val577), was significantly increased in Japanese patients with Sjögren’s syndrome (SS) and had a strong association with SS-A=Ro antibody production. In the present study, it was investigated whether the association of TAP2*Bky2 with SS-A=Ro antibody production was also found in Japanese patients with systemic lupus erythematosus (SLE). Polymorphisms of the TAP1 and TAP2 genes were determined in 114 Japanese SLE patients by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) method. The allele frequencies of the TAP1 and TAP2 genes in SLE patients were not significantly different from those in controls, although the allele frequency of TAP2*Bky2 was slightly higher in SLE patients than in healthy control subjects (9.2% vs 5.5%, P = 0.126). The allele frequency of TAP2*Bky2 was significantly higher in SLE patients with oral ulcers than in those without. It was noteworthy that TAP2*Bky2 was significantly associated with the appearance of not only SS-A=Ro antibody but also SS-B=La, nRNP, and Sm antibodies in the patients. The association of TAP2*Bky2 was found with the antibody production to both 60 and 52 kDa SS-A=Ro antigens. As TAP2*Bky2 had a strong linkage disequilibrium with DRB1*08032, TAP2*Bky2 or its haplotype with DRB1*08032 may be involved in SS-A=Ro antibody production not only in SS but also SLE patients, indicating that TAP2*Bky2 may be a susceptible gene not only to the disease of SS but also to the SS-A=Ro autoantibody production.
Acute renal failure complicating HELLP syndrome, SLE and anti-phospholipid syndrome: successful outcome using plasma exchange therapy
Authors: Roberts G , Gordon M M , Porter D , Jardine A G , Gibson I W
Published: April 2003

Renal disease is very common in patientswith systemic lupus erythematosis(SLE) and it may emerge during pregnancy or the post-partumperiod. Patients with anti-phospholipidsyndrome (APS) are also at risk of renal disease.We present a case of acute renal failure in the post-partumperiod in a patient with SLE and APS. This case illustrates the potential difficulties in reaching a diagnosis in such a patient. It also illustrates the complexities of management and the potential interactionsbetween SLE, Haemolysis, elevated liver enzymes and low platelets syndrome, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome and APS. We also review the role of plasma exchange therapy in managing our patient.
Systemic lupus erythematosus in the far north of Queensland
Authors: Bossingham D
Published: April 2003

An assessment of prevalence for systemic lupus erythematosus (SLE) has been attempted for the population of far north Queensland in Australia. This huge area has a majority Caucasian population living in a tropical environment. Roughly 10% of the population comprizes people of Australian Aboriginal or Torres Strait Islander descent. The prevalence of disease was high (45.3 per 100 000) overall and particularly so in the indigenous population (92.8 per 100 000) where the disease appears to be more severe. The pattern of organ involvement and laboratory anomalies did not vary between the populationsexamined. Disease duration however was different, being longer by comparison in the Caucasian population due to many premature deaths in the indigenous groups. The reasons for such high prevalencefigures and some problems encountered in practice are discussed.
Ethical Considerations in International Nursing Research: a report from the international centre for nursing ethics
Authors:   Working Group for the Study of Ethical Issues in International Nursing Research, Olsen Chair Douglas P
Published: April 2003

Ethical issues in international nursing research are identified and the perspectives of the International Centre for Nursing Ethics are offered in an effort to develop an international consensus of ethical behaviour in research. First, theoretical issues are reviewed, then initial conditions for ethical conduct are defined, and protocol design and procedure considerations are examined. A concerted effort is made to identify and avoid a western bias. Broad guiding principles for designing and reviewing research are offered: (1) respect for persons; (2) beneficence; (3) justice; (4) respect for community; and (5) contextual caring. A collaborative model of the researcher-participant relationship is suggested and discussed.
The Ethics of the Caring Conversation
Authors: Fredriksson Lennart , Eriksson Katie
Published: April 2003

The aim of this study was to explore the ethical foundations for a caring conversation. The analysis is based on the ethics of Paul Ricoeur and deals with questions such as what kind of person the nurse ought to be and how she or he engages in caring conversations with suffering others. According to Ricoeur, ethics (the aim of an accomplished life) has primacy over morality (the articulation of aims in norms). At the ethical level, self-esteem and autonomy were shown to be essential for a person (nurse) to act with respect and responsibility. The ethical relationship of a caring conversation was found to be asymmetrical, because of the passivity inflicted by suffering. This asymmetry was found to be potentially unethical if not balanced with reciprocity. In the ethical context, the caring conversation is one in which the nurse makes room through the ethos of caritas for a suffering person to regain his or her self-esteem, and thus makes a good life possible.
Differences in Ethical Attitudes Between Registered Nurses and Medical Students
Authors: Elder Ruth , Price John , Williams Gail
Published: April 2003

In this study we compared the ethical attitudes of a group of experienced, predominantly female, registered nurses (n = 67) with those of a group of final year, mixed sex, medical students (n = 125). The purpose was to determine the basis of differences in attitudes that could lead to ethical disagreements between these two groups when they came to work together. A questionnaire developed to explore ethical attitudes was administered and the responses of the two groups were compared using t-tests. Because of the preponderance of females among the nurses an analysis of variance of the gender-adjusted scores for each group was also carried out. On comparing the responses, the nurses differed significantly from the medical students in a number of ethical domains. A potential source of conflict between these two groups is that the nurses were inclined to adopt the perspective of patients but the medical students identified with their profession. When corrected for the effects of gender, the differences persisted, indicating that it was discipline that determined the differences. We recommend that students of nursing and medicine receive ethics education together, and that more open dialogue between doctors and nurses with respect to their different ethical viewpoints is needed in the work setting. This article will be of interest to educators of students of medicine and nursing, as well as to doctors and nurses who are eager to improve their professional relations and thereby improve patient care.
Moral Agency in Nursing: seeing value In the work and believing that i make a difference
Authors: Pask Elizabeth J
Published: April 2003

The subject of this article is moral agency in nursing, studied by the use of an applied philosophical method. It draws upon nurses’ accounts of how they see intrinsic value in their work and believe that they make a difference to patients in terms that leave their patients feeling better. The analysis is based on the philosophy of Iris Murdoch to reveal how nurses’ accounts demonstrated that they hold a view of themselves and their professional practice that is intrinsically linked to, and dependent upon, their capacity to see good in the work they do.
Ethical Issues After the Disclosure of a Terminal Illness: Danish and Norwegian hospice nurses’ reflections
Authors: Lorensen Margarethe , Davis Anne J , Konishi Emiko , Bunch Eli H
Published: April 2003

This research explored the ethical issues that nurses reported in the process of elaboration and further disclosure after an initial diagnosis of a terminal illness had been given. One hundred and six hospice nurses in Norway and Denmark completed a questionnaire containing 45 items of forced-choice and open-ended questions. This questionnaire was tested and used in three countries prior to this study; for this research it was tested on Danish and Norwegian nurses.

All respondents supported the ethics of ongoing disclosure to terminally ill patients based on ethical principles embedded in their country’s Patients’ Rights Acts. Truth, as an intrinsic value, proved foundational to patient autonomy, the most frequent ethical principle these nurses reported to justify their ethical position on information disclosure to terminally ill people. Telling the truth about a diagnosis was not the end of ethics in hospice care, but rather the beginning because what occurs ethically in dealing with prognosis issues became central to these hospice nurses, the patients and their families. Coupled with truth-telling, compassionate interaction and care become extensions of patients’ rights.
Conflicts of Interest: experiences of close relatives of patients suffering from amyotrophic lateral sclerosis
Authors: Bolmsjö Ingrid , Hermerén Göran
Published: April 2003

It is well known that close relatives of terminally ill patients endure great emotional stress. Many factors, such as existential concerns, contribute to the distress of these relatives. In this study, interviews were conducted to explore experiences concerning life restrictions, emotional distress, and limited support, in a group of close relatives of patients with amyotrophic lateral sclerosis (ALS). The purpose was to identify, illuminate and clarify ethical problems related to these experiences. The results indicate that close relatives of patients with ALS need someone to talk to, as well as more information about the disease and its process. Furthermore, the study illustrates how ethical problems are related to choices and conflicts, and that a process including shared decision making is often an ideal when trying to find a solution to ethical problems.
‘No-suicide Contracts’ and Informed Consent: an analysis of ethical issues
Authors: Farrow Tony L , O’Brien Anthony J
Published: April 2003

The ‘no-suicide contract’ is a frequently utilized tool in both the assessment and dispersal of suicidal patients. However, little attention has been given to questioning whether suicidal persons are able to give informed consent to enter such a contract. This article utilizes both the existing literature on no-suicide contracts and the results of recent research into the effects of this tool, to examine whether its use is consistent with the legal and ethical doctrine of informed consent. Particular attention is given to issues of competence, fullness of information, voluntariness and paternalistic intervention when no-suicide contracts are used. This analysis finds the tool to be problematic and suggests that individual patients’ ability to give informed consent about a no-suicide contract needs to be carefully considered by clinicians.
Reflections on the Health Workers’ Strike at Malawi’s Major Tertiary Hospital, QECH, Blantyre, 2001: a case study
Authors: Muula A S , Phiri A
Published: April 2003

Health workers and support staff at Malawi’s major referral hospital, the Queen Elizabeth Central Hospital, Blantyre, were on strike between 5th and 19th October 2001. The health workers’ grievances included: lack of risk allowances; poor professional allowances; low salaries; and low housing allowances. The strike resulted in almost total closure of the 1500-bed hospital; only the burns and orthopaedic wards continued to serve patients. Volunteer staff, comprising the Red Cross, and nursing and medical students provided services. Verbal and written threats by the authorities had minimal effect on terminating the strike; rather, they encouraged the resolve to continue with the industrial action. We report aspects of the genesis, progress and resolution of the strike. Although not much seems to have been achieved, both the employer and the workers need to draw lessons from the experience.
Cost of Migration: Invasion of Malignant Gliomas and Implications for Treatment
Authors: Giese A. , Bjerkvig R. , Berens M.E. , Westphal M.
Published: April 2003

Tumors of glial origin consist of a core mass and a penumbra of invasive, single cells, decreasing in numbers towards the periphery and still detectable several centimeters away from the core lesion. Several decades ago, the diffuse nature of malignant gliomas was recognized by neurosurgeons when super-radical resections using hemispherectomies failed to eradicate these tumors. Local invasiveness eventually leads to regrowth of a recurrent tumor predominantly adjacent to the resection cavity, which is not significantly altered by radiation or chemotherapy. This raises the question of whether invasive glioma cells activate cellular programs that render these cells resistant to conventional treatments. Clinical and experimental data demonstrate that glioma invasion is determined by several independent mechanisms that facilitate the spread of these tumors along different anatomic and molecular structures. A common denominator of this cellular behavior may be cell motility. Gene-expression profiling showed upregulation of genes related to motility, and functional studies demonstrated that cell motility contributes to the invasive phenotype of malignant gliomas. There is accumulating evidence that invasive glioma cells show a decreased proliferation rate and a relative resistance to apoptosis, which may contribute to chemotherapy and radiation resistance. Interestingly, interference with cell motility by different strategies results in increased susceptibility to apoptosis, indicating that this dynamic relationship can potentially be exploited as an anti-invasive treatment paradigm. In this review, we discuss mechanisms of glioma invasion, characteristics of the invasive cell, and consequences of this cellular phenotype for surgical resection, oncologic treatments, and future perspectives for anti-invasive strategies.
Disseminated Neuroblastoma in Children Older Than One Year at Diagnosis: Comparable Results With Three Consecutive High-Dose Protocols Adopted by the Italian Co-Operative Group for Neuroblastoma
Authors: De Bernardi Bruno , Nicolas Brigitte , Boni Luca , Indolfi Paolo , Carli Modesto , Cordero di Montezemolo Luca , Donfrancesco Alberto , Pession Andrea , Provenzi Massimo , di Cataldo Andrea , Rizzo Antonino , Tonini Gian Paolo , Dallorso Sandro , Conte Massimo , Gambini Claudio , Garaventa Alberto , Bonetti Federico , Zanazzo Andrea , D’Angelo Paolo , Bruzzi Paolo
Published: April 2003

Purpose: To compare the outcomes associated with modifications in three consecutive protocols employed by the Italian Co-Operative Group for Neuroblastoma (ICGNB) in disseminated neuroblastoma.

Patients and Methods: Between January 1985 and November 1997, a total of 359 children aged 1 to 15 years with newly diagnosed stage 4 neuroblastoma were enrolled in three consecutive protocols. Compared with ICGNB-85, the ICGNB-89 protocol contained two more chemotherapy cycles, and some drugs were given at greater doses, whereas in the ICGNB-92 protocol, the induction phase included a chelating agent, and individual cycles contained four drugs instead of two.

Results: A total of 330 of 359 evaluable children were included in this analysis; 106 children were treated with ICGNB-85, 65 children were treated with ICGNB-89, and 159 children were treated with ICGNB-92 protocols. Radical resection of primary tumor was carried out in 59.4%, 50.8%, and 57.9% of the patients, respectively. Major tumor response after induction therapy was achieved in 66.7%, 69.2%, and 68.6% of the patients, respectively. A total of 218 of 232 patients received consolidation therapy consisting of conventional chemotherapy in 65 patients and of high-dose chemotherapy in 153 patients. Disease recurrence or progression occurred in 82.1%, 69.2%, and 74.8% of the patients, respectively. Therapy-related deaths occurred in 1.9%, 12.3%, and 6.9% of the patients, respectively. Five-year overall survival (OS) for the three studies was 26%, 23%, and 28%, and event-free survival (EFS) was 19%, 17%, and 17%, respectively.

Conclusion: The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.
Leptin Distribution and Metabolism in the Pregnant Rat: Transplacental Leptin Passage Increases in Late Gestation but Is Reduced by Excess Glucocorticoids
Authors: Smith Jeremy T. , Waddell Brendan J.
Published: April 2003

Leptin is essential for the establishment of pregnancy and appears to promote fetal growth, but the mechanisms regulating fetal leptin exposure remain unclear. In rodents, indirect evidence suggests that fetal leptin is partly derived from the maternal circulation via transplacental passage. Indeed, the placenta expresses mRNA for Ob-Ra, one of the short forms of the leptin receptor (Ob-RS) important in leptin transport, and this expression increases markedly in late pregnancy. Therefore, we determined the transplacental passage of maternal leptin to the fetus in the rat and whether this transport increases near term in association with a rise in placental expression of Ob-RS protein. Because of the proposed role of leptin in promoting fetal growth, we also assessed the effect of glucocorticoid-induced fetal growth retardation on placental leptin transport. Anesthetized rats received a constant infusion of 125I-leptin via a jugular cannula before and at d 16 and 22 of pregnancy (term = d 23); plasma samples were obtained at 10, 20, 40, 60, 80, and 100 min, and fetuses and placentas were collected at the time of the final sample. The metabolic clearance rate of leptin fell (P < 0.01) from 3.08 ± 0.23 ml/min per kg in nonpregnant rats to 2.36 ± 0.13 ml/min per kg by d 22. Transplacental passage of 125I-leptin, estimated from its concentration in the whole fetus relative to maternal plasma, increased 10-fold (P < 0.005) between d 16 and d 22 of pregnancy. Over this same period, Ob-RS protein expression in the placental labyrinth zone increased by almost 2-fold. Transplacental leptin passage was reduced (P < 0.05) by 77% after maternal dexamethasone treatment, whereas suppression of endogenous glucocorticoid synthesis (by metyrapone) increased (P < 0.05) the transfer of maternal leptin to the fetus by 55%. These data show that transplacental passage of maternal leptin is a significant source of fetal leptin and increases markedly during late pregnancy. Consistent with the proposed role of leptin as a fetal growth factor, transplacental leptin passage is reduced in association with glucocorticoid-induced fetal growth retardation.
Structural Analysis of Yoked Chorionic Gonadotropin-Luteinizing Hormone Receptor Ectodomain Complexes by Circular Dichroic Spectroscopy
Authors: Fralish Gregory B. , Dattilo Brian , Puett David
Published: April 2003

Binding of the heterodimeric glycoprotein hormone, chorionic gonadotropin (CG), occurs to the heptahelical LH receptor N-terminal ectodomain (ECD), a large portion of which has been modeled as a leucine-rich repeat protein. In this study, we expressed and purified three single chain N-CG-ECD-C complexes, one comprising the full-length ECD, 1–341 (encoded by exons 1–10 and a portion of 11), and two C-terminal ECD deletion fragments, 1–294 (encoded by exons 1–10) and 1–180 (encoded by exons 1–7). The fusion proteins, including yoked CG (N-β-α-C), were characterized by Western blot analysis and circular dichroism (CD). Analysis of the CD spectra obtained on the CG-ECD fusion proteins, and of the difference spectrum of each after subtracting the CG contribution, yielded secondary structures consistent with a repeating β-strand/α-helix fold as predicted in the homology model. A marked decrease in helicity was observed when the C-terminal 47 amino acid residues were removed from the ECD. Removal of an additional 114 residues, i.e. the region encoded by exons 8–10, results in the loss of fewer helical residues. These results suggest that the hinge region of the ECD, predicted to contain only limited secondary structure, interacts with and stabilizes the ligand-occupied N-terminal portion. Furthermore, the results support a repeating fold, consistent with the proposed model for the LHR ECD.
Regulated secretion: SNARE density, vesicle fusion and calcium dependence
Authors: Coorssen Jens R. , Blank Paul S. , Albertorio Fernando , Bezrukov Ludmila , Kolosova Irina , Chen Xiongfong , Backlund Peter S. , Zimmerberg Joshua
Published: April 2003

SNAREs such as VAMP, SNAP-25 and syntaxin are essential for intracellular trafficking, but what are their exact molecular roles and how are their interactions with other proteins manifest? Capitalizing on the differential sensitivity of SNAREs to exogenous proteases, we quantified the selective removal of identified SNAREs from native secretory vesicles without loss of fusion competence. Using previously established fusion assays and a high sensitivity immunoblotting protocol, we analyzed the relationship between these SNARE proteins and Ca2+-triggered membrane fusion. Neither the extent of fusion nor the number of intermembrane fusion complexes per vesicle were correlated with the measured density of identified egg cortical vesicle (CV) SNAREs. Without syntaxin, CVs remained fusion competent. Surprisingly, for one (but not another) protease the Ca2+dependence of fusion was correlated with CV SNARE density, suggesting a native protein complex that associates with SNAREs, the architecture of which ensures high Ca2+ sensitivity. As SNAREs may function during CV docking in vivo, and as further proteolysis after SNARE removal eventually ablates fusion, we hypothesize that the triggered steps of regulated fusion(Ca2+ sensitivity and the catalysis and execution of fusion)require additional proteins that function downstream of SNAREs.
Regulation of tight junctions during the epithelium-mesenchyme transition:direct repression of the gene expression of claudins/occludin by Snail
Authors: Ikenouchi Junichi , Matsuda Miho , Furuse Mikio , Tsukita Shoichiro
Published: April 2003

Snail is a transcription repressor that plays a central role in the epithelium-mesenchyme transition (EMT), by which epithelial cells lose their polarity. Claudins and occludin are integral membrane proteins localized at tight junctions, which are responsible for establishing and maintaining epithelial cell polarity. We examined the relationship between Snail and the promoter activity of claudins and occludin. When Snail was overexpressed in cultured mouse epithelial cells, EMT was induced with concomitant repression of the expression of claudins and occludin not only at the protein but also at the mRNA level. We then isolated the promoters of genes encoding claudins and occludin, in which multiple E-boxes were identified. Transfection experiments with various promoter constructs as well as electrophoretic mobility assays revealed that Snail binds directly to the E-boxes of the promoters of claudin/occludin genes, resulting in complete repression of their promoter activity. Because the gene encoding E-cadherin was also reported to be repressed by Snail, we concluded that EMT was associated with the simultaneous repression of the genes encoding E-cadherin and claudins/occludin (i.e. the expression of adherens and tight junction adhesion molecules,respectively).