In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.     

A coordinated strategy for evaluating new vaccines for human and animal tuberculosis.

There is a remarkable convergence in the current efforts to develop and evaluate new tuberculosis (TB) vaccine candidates for use in humans, domestic animals, and wild animal reservoirs. It is quite likely that similar vaccination strategies will prove useful in these diverse host species. Many TB vaccine candidates are being screened for protective efficacy in conventional laboratory animals (e.g. mouse, guinea pig), in captive wild species under laboratory conditions (e.g. brushtail possum), and in the target hosts (e.g. cattle, deer). These systems share some important features, e.g. direct challenge infection of the lung by intratracheal or aerosol exposure, and the use of bacterial enumeration, and gross and microscopic histopathology, as the readouts. Some TB vaccine candidates have been tested in many models, yielding important insights into common mechanisms of resistance to Mycobacterium tuberculosis and M. bovis, and providing evidence of the vaccine's ability to induce protection under widely different circumstances. Coordination of this global search for better TB vaccines, irrespective of target species, would facilitate the rapid application of new technologies and maximize the sharing of materials and experiences between human and veterinary TB researchers. The creation of liaisons between TB vaccine research efforts of government-sponsored medical and agricultural research programs, international bodies such as the World Health Organization (WHO) and the European Community (EC), private foundations and the vaccine industry, will yield a high return.     

Lues and lupus: syphilis mimicking systemic lupus erythematosus (SLE)

Malar rash and photosensitivity are common findings in systemic lupus erythematosus (SLE). However, a number of inflammatory, dermatologic, infectious or drug-induced conditions may mimic cutaneous findings of SLE. These typically include seborrheic dermatitis, contact dermatitis, rosacea, polymorphous light eruption, syphilis and dermatomyositis sine myositis. Herein we describe a patient with fever, malar rash, alopecia, photosensitivity, arthralgias and lymphadenopathy who was subsequently diagnosed with secondary syphilis. In this case report we review clinical and histopathological findings in the differential diagnosis of malar rash and photosensitivity and discuss the overlapping features of syphilis and SLE.     

Employment status at time of first hospitalization for heart failure is associated with a higher risk of death and rehospitalization for heart failure

Aims

Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self‐perceived and objective health status. In this study, we examined the association between employment status and the risk of all‐cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF.

Methods and results

We identified all patients of working age (18–60 years) with a first HF hospitalization in the period 1997–2015 in Denmark, categorized according to whether or not they were part of the workforce at time of the index admission. The primary outcome was death from any cause and the secondary outcome was readmission for HF. Cumulative incidence curves, binomial regression and Cox regression models were used to assess outcomes. Of 25 571 patients with a first hospitalization for HF, 15 428 (60%) were part of the workforce at baseline. Patients in the workforce were significantly younger (53 vs. 55 years) more likely to be male (75% vs 64%) and less likely to have diabetes (13% vs 22%) and chronic obstructive pulmonary disease (5% vs 10%) (all P < 0.0001). Not being part of the workforce was associated with a significantly higher risk of death [hazard ratio (HR) 1.59; 95% confidence interval (CI) 1.50–1.68] and rehospitalization for HF (HR 1.09; 95% CI 1.05–1.14), in analyses adjusted for age, sex, co‐morbidities, education level, calendar time, and duration of first HF hospitalization.

Conclusion

Not being part of the workforce at time of first HF hospitalization was independently associated with increased mortality and recurrent HF hospitalization.

     

Synovial fluid copper and related variables in rheumatoid and degenerative arthritis.

Copper, caeruloplasmin, transferrin, albumin, and total protein were measured in the serum and synovial fluid of 40 patients with rheumatoid arthritis and 40 patients with osteoarthrosis. A raised synovial fluid copper and caeruloplasmin have been found to be characteristic of rheumatoid effusions. The relation between copper and caeruloplasmin in synovial fluid differs from that in serum. Synovial fluid caeruloplasmin was increased disproportionately in relation to other plasma proteins present in rheumatoid effusions.     

A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study

PURPOSE: To describe the effect of atrial fibrillation on long-term morbidity and mortality. SUBJECTS AND METHODS: The Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45-64 years between 1972 and 1976. All hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions. RESULTS: After 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval [CI]: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95% CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3-4.8) for strokes, and 3.4 (95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men (RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95% CI: 0.9-3.8). CONCLUSIONS: Atrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women.