Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis

In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa‐B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune‐mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5–1.0 × 10⁶ cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M‐CSF as controls. Tartrate‐resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M‐CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.     

Interhemispheric visual competition after multisensory reversal of hemianopia

Unilateral lesions of visual cortex have the secondary consequence of suppressing visual circuits in the midbrain superior colliculus (SC), collectively producing blindness in contralesional space (“hemianopia”). Recent studies have demonstrated that SC visual responses and contralesional vision can be reinstated by a non‐invasive multisensory training procedure in which spatiotemporally concordant visual‐auditory pairs are repeatedly presented within the blind hemifield. Despite this recovery of visual responsiveness, the loss of visual cortex was expected to result in permanent deficits in that hemifield, especially when visual events in both hemifields compete for attention and access to the brain's visuomotor circuitry. This was evaluated in the present study in a visual choice paradigm in which the two visual hemifields of recovered cats were simultaneously stimulated with equally valent visual targets. Surprisingly, the expected disparity was not found, and some animals even preferred stimuli presented in the previously blind hemifield. This preference persisted across multiple stimulus intensity levels and there was no indication that animals were less aware of cues in the previously blind hemifield than in its spared counterpart. Furthermore, when auditory cues were combined with visual cues, the enhanced performance they produced on a visual task was no greater in the normal than in the previously blind hemifield. These observations suggest that the multisensory rehabilitation paradigm revealed greater inherent visual information processing potential in the previously blind hemifield than was believed possible given the loss of visual cortex.     

Action research methodology in clinical pharmacy: how to involve and change

Introduction The focus in clinical pharmacy practice is and has for the last 30–35 years been on changing the role of pharmacy staff into service orientation and patient counselling. One way of doing this is by involving staff in change process and as a researcher to take part in the change process by establishing partnerships with staff. On the background of the authors’ widespread action research (AR)-based experiences, recommendations and comments for how to conduct an AR-study is described, and one of their AR-based studies illustrate the methodology and the research methods used. Methodology AR is defined as an approach to research which is based on a problem-solving relationship between researchers and clients, which aims at both solving a problem and at collaboratively generating new knowledge. Research questions relevant in AR-studies are: what was the working process in this change oriented study? What learning and/or changes took place? What challenges/pitfalls had to be overcome? What were the influence/consequences for the involved parts? When to use If you want to implement new services and want to involve staff and others in the process, an AR methodology is very suitable. The basic advantages of doing AR-based studies are grounded in their participatory and democratic basis and their starting point in problems experienced in practice. Limitations Some of the limitations in AR-studies are that neither of the participants in a project steering group are the only ones to decide. Furthermore, the collective process makes the decision-making procedures relatively complex.

     

Incidence rates of acute promyelocytic leukemia among Hispanics, blacks, Asians, and non-Hispanic whites in the United States.

Despite significant improvements in the prognosis of acute promyelocytic leukemia brought about by therapeutic advances, understanding of the epidemiology of acute promyelocytic leukemia remains limited. Earlier reports have suggested that Hispanics may have an increased incidence of acute promyelocytic leukemia, but no systematic analysis of national data has yet been reported. We performed a retrospective cohort study, using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 1992-2001 in order to compare leukemia incidence rates as a function of race and ethnicity. We identified 709 cases of acute promyelocytic leukemia and analyzed incidence rates by race and sex. Hispanics were not found to have greater lifetime incidence rates than whites, with an incidence relative rate (IRR) of 0.86 that of whites (P=0.17). The age distribution among Hispanics was significantly different from non-Hispanic whites, with greater incidence rates for children ages 1-19 years (IRR=1.9, P=0.02) and adult ages 20-44 years (IRR=1.6, P=0.004). Blacks had lower lifetime incidence rates than non-Hispanic whites (IRR=0.75, P=0.04), Hispanics (IRR=0.64, P=0.007), and Asians (IRR=0.67, P=0.03). Asians did not differ from non-Hispanic whites in lifetime or age-specific incidence rates. These results indicate that while US Hispanics do not have greater lifetime incidence rates of acute promyelocytic leukemia, blacks have lower incidence rates of acute promyelocytic leukemia than Hispanics, non-Hispanic whites, and Asians.     

Splenic injuries in children after blunt abdominal trauma

Management of splenic injuries in children has evolved over the past two decades. Splenectomies or splenorrhaphies are now performed infrequently, with the majority of hemodynamically stable children with splenic injuries managed nonoperatively. This article reviews the imaging features of acute splenic injuries in children as well as the appearance of healing splenic injuries. Follow-up evaluation and outcomes in children with splenic injuries also are addressed.     

A five-year prospective follow-up of women with non-obstructive pyelonephritic renal scarring

Fifty women with pyelonephritic renal scarring were prospectively followed for five years and the changes in renal function were related to blood pressure control, plasma renin activity, urinary albumin excretion and the incidence of urinary tract infections (UTI). Five patients (10%) developed end stage renal disease. All these patients had bilateral disease, proteinuria and anti-hypertensive treatment at presentation. The mean +/- SD glomerular filtration rate (GFR) of all patients with renal scarring was 74 +/- 27 ml/min x 1.73 m2 at presentation which was significantly lower than the GFR in 55 patients with a recent episode of acute pyelonephritis (p less than 0.001) and 10 healthy controls (p less than 0.001). GFR and age corrected GFR decreased significantly during follow-up (p less than 0.001) and p less than 0.02 respectively). The decrease in GFR was significantly higher in patients with bilateral scarring, in patients on blood pressure treatment and in patients with an episode of symptomatic UTI during follow-up. Eight patients (16%) had antihypertensive treatment at presentation and another 11 patients (26%), of whom 10 had bilateral scarring, developed hypertension (greater than 140/90 mmHg) during follow-up. Seventy-five per cent of all patients had symptomatic UTI and 40% had an episode of acute pyelonephritis during follow-up. In conclusion, patients with pyelonephritic scarring have a high incidence of UTI and are at high risk of developing renal failure and hypertension. It is essential that recurrent episodes of symptomatic UTI are treated promptly and that blood pressure is monitored carefully in these patients.     

Therapeutic Options for Chronic Hepatitis B: Considerations and Controversies

Five agents are currently approved for the treatment of chronic hepatitis B infection. This article will discuss the three agents for which the most extensive data are available; interferon (IFN), lamivudine, and adefovir, while the following article by Dr. Jules Dienstag will discuss the recently marketed agents, entecavir and peginterferon alfa-2a. The advantages of IFN are its finite duration of therapy (4–6 months), lack of emergence of resistance, and durability of response. On the negative side, response to IFN is less durable in patients with HBeAg-negative chronic hepatitis B virus (HBV). Also, use of IFN is limited by adverse effects and the mode of administration (daily to thrice-weekly subcutaneous injection). Lamivudine and adefovir are orally administered and have good tolerability and safety. Even in patients who experience a marked decrease in serum HBV DNA and loss of HBeAg, oral therapy needs to be continued for at least 6 months, to avoid the risk of reappearance of HBeAg and viremia. Rates of HBeAg seroconversion to anti-HBe-positivity increase with duration of lamivudine or adefovir therapy. The likelihood of development of resistance to lamivudine and associated viral breakthrough limits its long-term use. In patients with HBeAg-negative chronic hepatitis B, long-term therapy is usually required, as off-treatment relapse is common. The emergence of resistance to adefovir is delayed and infrequent, hence adefovir may be preferred in patients requiring long-term therapy.