Polymorphisms at the osteoprotegerin and interleukin-6 genes in relation to first-ever stroke

BACKGROUND: Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH). METHODS: We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association. RESULTS: Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19-6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71-21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes. CONCLUSIONS: In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.     

Up‐regulation of cytokines and chemokines predates the onset of rheumatoid arthritis

Objective

To identify whether cytokines, cytokine‐related factors, and chemokines are up‐regulated prior to the development of rheumatoid arthritis (RA).

Methods

A nested case–control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre‐patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre‐patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system.

Results

The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin‐1β [IL‐1β], IL‐2, IL‐6, IL‐1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon‐γ, IL‐12), Th2 cells (IL‐4, eotaxin), Treg cells (IL‐10), bone marrow–derived factors (IL‐7, granulocyte–macrophage colony‐stimulating factor, and granulocyte colony‐stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1α). The levels were particularly increased in anti–cyclic citrullinated peptide antibody– and rheumatoid factor–positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL‐17 in individuals before disease onset was significantly higher than that in patients after disease onset. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cells, Th2 cells, and Treg cell–related cytokines, while chemokines, stromal cell–derived cytokines, and angiogenic‐related markers separated patients after the development of RA from individuals before the onset of RA.

Conclusion

Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine‐related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell–related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.

     

To both be like a captain and fellow worker of the caring team: the meaning of Nurse Assistants' expectations of Registered Nurses in Swedish residential care homes

Aim.  To describe the expectations of and to illuminate the meaning of the Nurse Assistants' (NA) expectations of Registered Nurses (RN) who are responsible for the care of older people living in residential care homes in Sweden.
Background.  Older people in Sweden who are provided with residential care are extremely frail and incapable of independent living. Therefore, when providing care, RN and NA encounter older people who require a great deal of care. An important precondition for the provision of satisfactory care is to have adequate collaboration between NAs and RNs and their expectations of each other. In this paper, the focus is on the NAs expectations of the RNs.
Method.  The study is based on a qualitative approach and a phenomenological-hermeneutical method. Ten NAs were interviewed and asked to narrate as freely as possible, about their expectations of RNs. The narratives were audio taped and transcribed verbatim. The analytical process includes the following steps; naïve reading, structural analysis, comprehensive understanding and reflection.
Results.  The RNs were expected to take responsibility for being fellow human beings and experts in providing care as well as always available to participate in caring. The RNs were expected to make stand-alone decisions and create a sense of safety for both older people and the NAs and have the courage to work alone and create a safe environment for both the older people and the NAs. The meaning of these expectations was that the RNs are like a captain in providing care, but at the same time, fellow workers.
Conclusion.  When the RNs do not meet the NAs expectations, there is a risk of conflict and therefore also a risk that an unsafe environment being created when caring for older people.     

Esophageal cancer in Stockholm county 1978-1995

Background. Most studies regarding esophageal cancer are based on a selection of patients, influencing the prognosis as well as other variables measured. Sweden may be unique in that it has registries that cover the whole population, permitting population based studies regarding diseases such as esophageal cancer. This also makes it possible to study the true nature of a population of patients and to describe changes in that population over time. Method. Retrospective analysis of the files of all 1284 patients diagnosed with esophageal cancer in Stockholm County 1978-1995. The study period was divided into three six-year intervals (periods I, II and III). Results. A total of 201 patients were diagnosed at autopsy. They were only analyzed regarding histopathological and demographic parameters. A statistically significant increased survival for the whole group of patients was found, but this improvement in survival was not found among resected patients. No survival benefit was noted for patients operated on at large centers compared to patients operated on at surgical clinics with few yearly resections performed. The well-known increase in the incidence of adenocarcinoma in the esophagus among men was documented. A tendency (non-significant) of an increase in the incidence of adenocarcinoma among women was also noted. Conclusions. Survival seems to have increased among esophageal cancer patients, but this survival benefit is not dependent on improved surgery. The number of yearly operations in a clinic did not correlate to long-term survival in this study.     

Quality of life in asymptomatic children and adolescents before and after diagnosis of hypertrophic cardiomyopathy through family screening

Aims and objectives. The aim of this study was to measure quality of life (QoL) in asymptomatic children with hypertrophic cardiomyopathy (HCM) before and after diagnosis. Background. Hypertrophic cardiomyopathy is a disease with a 50% risk of inheritance. Children at risk for serious complications can be diagnosed early with family screening, but before embarking on a screening programme, it is important to evaluate the psychosocial consequences of such screening. Design. Prospective case‐control study. Methods. Quality of life was measured using a questionnaire by Lindström incorporating both objective and subjective aspects of the three spheres: external, interpersonal and personal, before and two years after diagnosis. The study group consisted of 13 children/adolescents (11 boys), median age 11 (5–18) years, with HCM diagnosed at family screening. All filled out a questionnaire before diagnosis and at follow‐up. 41 healthy children/adolescents (22 boys), median age 11 (2–19) years with a first‐degree relative diagnosed with HCM served as controls; 15/41 also completed follow‐up data. Results. The total QoL score for all spheres was similar in both groups at baseline and follow‐up. In the interpersonal sphere, it was more common that children diagnosed with HCM had no siblings both at baseline (p = 0·002) and follow‐up (p = 0·005). The family situation, social support and life events were unchanged from baseline to follow‐up. Children with HCM had significantly more psychosomatic symptoms compared with controls at baseline (p < 0·05) but not at follow‐up. Self‐esteem, peer acceptance and satisfaction with school were unchanged and similar between groups. Conclusion. Family screening for HCM does not appear to negatively influence QoL. Relevance to clinical practice. This study indicates that family screening of asymptomatic children and adolescents had no significant detrimental effects on QoL. This suggests that the benefits of finding symptomatic individuals at risk for serious complications outweigh concerns about screening asymptomatic individuals.     

C‐reactive protein and tumor necrosis factor‐alpha in relation to insulin‐mediated glucose uptake,smoking and atherosclerosis

Objectives. To examine the hypothesis that serum concentration of C‐reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor‐α (TNFα) and interleukin‐6 (IL‐6). Material and methods. Cross‐sectional, one‐center study of a population‐based sample of 58‐year‐old Swedish men (n = 98). Exclusion criteria were cardiovascular disease, clinical diabetes mellitus and/or continuous cardiovascular medication. Glucose infusion‐rate (euglycemic hyperinsulinemic clamp), adjusted for fat‐free mass, which together with total body fat was measured by dual‐energy X‐ray absorptiometry. Serum concentrations of CRP, TNFα, soluble TNFα receptor 2 (sTNFAR2), IL‐6 determined by ELISA. Ultrasound was used to measure intima‐media thickness (IMT) in both common carotid arteries, carotid bulbs and in the right femoral artery. Results. CRP was inversely associated with insulin sensitivity (r = ?0.28, p<0.01) and with total body fat (r = 0.31, p<0.01), but not independently of the TNFα and sTNFAR2 product. Serum CRP, TNFα, sTNFAR2, but not IL‐6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome. These associations were independent of smoking and carotid and femoral artery IMT. Conclusions. Serum concentrations of CRP were related to insulin sensitivity and accompanying factors constituting the metabolic syndrome. The results indicate that this association may be mediated by adipose tissue and TNFα effects, the latter measured as the product of TNFα and sTNFAR2. This was a cross‐sectional study and causality cannot be proven.     

Flow cytometric DNA ploidy defines patients with poor prognosis in node-negative breast cancer

Flow cytometric DNA analysis was performed on fine-needle aspirates from frozen tumour biopsies from 421 node-negative, non-adjuvantly-treated breast-cancer patients with a median observation time of 6.75 years. Among premenopausal patients (n = 175), those having at least one DNA “hypoploid” sub-population defined as DNA index (DI) <0.96 or 1.44 ≤ Dl < 1.92 (n = 81) were characterized by early recurrences (log-rank p = 0.05, Wilcoxon p = 0.007), poor overall survival (OS) (p < 0.001) and poor survival after recurrence (p < 0.001). In the postmenopausal group (n = 246), there were no significant differences among 7 different Dl classes regarding either recurrence-free survival (RFS) or OS. S-phase fraction (SPF), divided into quartiles, predicted OS in premenopausal patients only (p = 0.02). Conventional multivariate Cox analysis of OS in the premenopausal group revealed hypoploidy to be the only independent prognostic factor involving a relative risk (RR) of 22.8. Age ≤ 40 years was of marginal significance, whereas SPF, histological grade (WHO), oestrogen and progesterone receptor (PgR) content, tumour size and number of lymph nodes removed were excluded from the model. Application of the conventional Cox model to the premenopausal group regarding RFS was found inappropriate due to lack of proportionality of the hazards of hypoploidy, SPF and histological grade. However, introduction of time-dependent co-variates using 2 years as cut-off level showed hypoploidy with a RR of 3.52 and age ≤ 40 years with a RR of 3.28 to be independent prognostic factors. In the postmenopausal group, the conventional Cox model identified the number of lymph nodes removed to be the only independent prognostic factor regarding RFS as well as OS, whereas SPF < 9% (lowest quartile) was of marginal significance in RFS analysis. Hypoploidy was correlated to high SPF, low PgR content and low differentiation, indicating that hypoploid tumours proliferate rapidly and hormone-independently. These patients may therefore benefit from adjuvant chemotherapy administered while tumour burden and risk of drug resistance are still low. © 1994 Wiley-Liss, Inc.     

The nearest and dearest: a lifeline for ICU patients

This study was designed to examine, describe and elucidate patients' experiences of the presence and visits of the nearest and their participation in the care process during their stay in the ICU. Five patients, three men and two women, were interviewed for about one hour each. A hermeneutic approach was used when the texts from the interviews were interpreted and analysed. The theoretical frame of interpretation was based on Tillich's theory concerning 'The courage to be' and Eriksson's theory on 'Suffering'. It was found that suffering from severe disease or injury results in not only a threat against the person as an individual, but also against the individual as a part in the world, with consequent feelings of estrangement and the fear of meaninglessness. The threat can, however, be neutralized by the nearests' presence and visits. These represent fellowship, togetherness and participation and thus can help to maintain the patient's identity and individuality. By experiencing this, patients as individuals may be able to affirm themselves and their 'courage to be' will be given strength and support.     

Combined Treatment Modalities in Esophageal Cancer: Should chemotherapy be included?

The poor prognosis of esophageal carcinoma patients after treatment with local modalities (surgery/radiotherapy) is well known. The purpose of this review is to assess the question whether addition of chemotherapy to local treatment of squamous cell carcinoma of the esophagus has had any beneficial effect on treatment results. In the absence of a sufficient number of randomized trials addressing this issue, data mainly from single-arm studies are discussed. Compiled data from studies on preoperative chemotherapy, preoperative chemoradiation and chemoradiation without surgery suggest that addition of chemotherapy to local treatment (surgery/radiotherapy) might increase short-term survival (2 years) compared to local therapy alone. In the case of chemoradiation without surgery this conclusion is strengthened by results from randomized trials. In general lack of long-term follow-up data limits conclusion whether to recommend the inclusion of chemotherapy into treatment of esophageal cancer or not. Treatment results, however, from studies utilizing combination chemotherapy given concomitant with radiotherapy support the contention that well-designed randomized trials with long-term follow-up should be performed. Outside controlled trials, however, surgery or radiotherapy should still be regarded as standard treatment modalities.