Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells

Multiple myeloma (MM) is characterized by almost exclusive tropism of malignant cells for the bone marrow (BM) milieu. The survival and proliferation of malignant plasma cells have been shown to rely on interactions with nonmalignant stromal cells, in particular mesenchymal stromal cells (MSCs), in the BM microenvironment. However, the BM microenvironment is composed of a diverse array of cell types. This study examined the role of macrophages, an abundant component of BM stroma, as a potential niche component that supports malignant plasma cells. We investigated the proliferation of MM tumour cell lines when cultured alone or together with MSCs, macrophages, or a combination of MSCs and macrophages, using the carboxyfluorescein succinimidyl ester assay. Consistently, we observed increased proliferation of MM cell lines in the presence of either MSCs or macrophages compared to cell line-only control. Furthermore, the combined co-culture of MSCs plus macrophages induced the greatest degree of proliferation of myeloma cells. In addition to increased proliferation, MSCs and macrophages decreased the rate of apoptosis of myeloma cells. Our in vitro studies provide evidence that highlights the role of macrophages as a key component of the BM microenvironment facilitating the growth of malignant plasma cells in MM.     

Molecular immune responses of the mosquito Anopheles gambiae to bacteria and malaria parasites

Immune responses of the malaria vector mosquito Anopheles gambiae were monitored systematically by the induced expression of five RNA markers after infection challenge. One newly isolated marker encodes a homologue of the moth Gram-negative bacteria-binding protein (GNBP), and another corresponds to a serine protease-like molecule. Additional previously described markers that respond to immune challenge encode the antimicrobial peptide defensin, a putative galactose lectin, and a putative serine protease. Specificity of the immune responses was indicated by differing temporal patterns of induction of specific markers in bacteria-challenged larvae and adults, and by variations in the effectiveness of different microorganisms and their components for marker induction in an immune-responsive cell line. The markers exhibit spatially distinct patterns of expression in the adult female mosquito. Two of them are highly expressed in different regions of the midgut, one in the anterior and the other in the posterior midgut. Marker induction indicates a significant role of the midgut in insect innate immunity. Immune responses to the penetration of the midgut epithelium by a malaria parasite occur both within the midgut itself and elsewhere in the body, suggesting an immune-related signaling process.     

Effect of Atrial Pressure Increase on Effective Refractory Period and Vulnerability to Atrial Fibrillation in Patients with Lone Atrial Fibrillation

Background: There is evidence suggesting that atrial fibrillation (AF) may be induced by acute increase of atrial pressure. The aim of the present study was to investigate the effect of alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness, and on the frequency of induction of (AF), in patients with a history of lone atrial fibrillation (LAF).Methods and Results: Twenty-five patients were included in this study. The patients were divided in two groups: the LAF group, and the control group. None of the patients in either group had organic heart disease. Effective refractory period (ERP) and duration of atrial extrastimulus electrogram (A₂) were measured at two right atrial sites (high lateral wall, atrial appendage) during AV pacing (cycle length: 500 msec) with different AV intervals. Peak, minimal and mean atrial pressure increased from 8.57 ± 2.37 to 18.14 ± 4.74 mm Hg, 2 ± 2.23 to 5.14 ± 2.60 mm Hg (p = 0.0001) and from 4.28 ± 1.6 mm Hg to 9.77 ± 2.9 mm Hg (p = 0.001), respectively during AV interval modification. During lateral and atrial appendage pacing, with a progressive decrease of AV interval to 160, 100, 80, 40, 0 msec, the ERP, the dispersion of ERP, functional refractory period (FRP), A2 and latency period (LP) did not change significantly, in both groups. The frequency of induction of AF was not statistically different in both lateral atrial wall and appendage, during pacing in different AV intervals.Conclusions: This study demonstrates that alterations in the intraatrial pressure does not have important effects on atrial refractoriness and does not increase vulnerability to AF in patients with a history of LAF.     

Percutaneous endoscopic gastrostomy as a tool to assist pneumatic dilation in a difficult case of sigmoid esophagus

We describe a case of a long-standing, untreated achalasia with a huge sigmoid esophagus in a 58-year-old Caucasian man who declined surgery. All means of classical endoscopic approach for pneumatic dilation, including the use of an overtube, were impossible because any attempt to propel the balloon dilator made the guide wire pull back out of the stomach because of the large loops and the tortuosity of the esophagus. For this reason, we used, for the first time, a combined approach of percutaneous gastrostomy and endoscopy in order to fix the guide wire at two points, achieving a pneumatic dilation in this way. A few months later, a significant improvement in the symptoms and nutritional status of the patient were observed.     

Coronary and peripheral blood flow changes following biventricular pacing and their relation to heart failure improvement.

AIMS: To study the effect of cardiac resynchronization therapy (CRT) on coronary and peripheral arterial circulation and to assess whether their changes are related to the improvement in patients' functional capacity and prognostically important biochemical markers. METHODS AND RESULTS: Twenty-five patients were studied (New York Heart Association classes III and IV, left ventricular ejection fraction <35%, QRS>120 ms, mean age 66 +/- 2.1 years). Coronary blood flow (CBF), forearm blood flow (FBF), and their reserve were measured by transoesophageal echocardiography (in cm/s) and venous occlusion plethysmography (in mL/100 mL/min) at baseline and following 3 months of CRT. N-terminal-pro-brain natriuretic peptide (Nt-pro-BNP) and serum adhesion molecules, sICAM-1 and sVCAM-1 levels were also assessed. CRT induced a non-significant increase in resting CBF (baseline vs. CRT: 52.1 +/- 5.5 vs. 58.2 +/- 3.6, P: NS), whereas hyperaemic CBF was increased by CRT (baseline vs. CRT: 67.8 +/- 6.8 vs. 79.8 +/- 6.2, P < 0.05). Significant increases were observed in resting FBF (baseline vs. CRT: 1.6 +/- 0.2 vs. 2.6 +/- 0.2, P < 0.05) and hyperaemic FBF (baseline vs. CRT: 2.1 +/- 0.2 vs. 3.2 +/- 0.3, P < 0.05). The per cent difference in hyperaemic FBF was related to the per cent change in Nt-pro-BNP (r = -0.71, P < 0.05) and the per cent improvement in exercise duration (r = 0.80, P < 0.05). CONCLUSION: CRT induces favourable changes in coronary and peripheral arterial function. Changes in peripheral blood flow are related to patients' improvement and may be prognostically significant.     

Impact of the longitudinal quantitative assessment of juvenile systemic lupus erythematosus severity on the disease outcome

Clinical Rheumatology - This study on juvenile SLE patients aimed to evaluate retrospectively the impact of a tertiary center’s management policy of the disease severity on its long-term...     

Alcohol in Mayan Guatemala: consumption, distribution, production and composition of cuxa

Aims   To describe the consumption, distribution, production and chemical composition of alcohol, including cuxa (pronounced 'coo sha'), in Nahualá, a highland Mayan municipality in Guatemala. Cuxa is a sugarcane-derived spirit, in part produced clandestinely, that has been distributed in the community for several decades.
Methods   Key informant interviews with alcohol distributors and consumers, cuxa producers and health professionals, as well as analyses of questionnaires from a sample of 47 spouses who came to the local health centre for problems related to their husband's drinking. Sampling and chemical analysis of cuxa from 12 of 13 identified sales points in the head-town of Nahualá and its nearby settlements (10 km radius). Fieldwork was conducted between November 2007 and March 2008.
Results   Alcohol consumption was found to be integrated culturally in this community. The overall drinking culture was marked by irregular heavy drinking occasions, especially around market days, with substantial inebriation and health problems, especially among street inhabiting drinkers. Cuxa contributed to these problems, and cuxa drinking was socially stigmatized. Cuxa was produced both clandestinely and industrially, and sold legally by taverns and illegally by clandestine distributors. The alcoholic strength of the samples was typically between 17 and 19% vol.; clandestinely produced cuxa samples showed acetaldehyde contamination.
Conclusions   Measures should be taken to reduce the harm associated with alcohol in this community, including efforts to reduce acetaldehyde levels in cuxa.     

Plasma Exchange in Patients with Toxic Epidermal Necrolysis

Abstract: We describe our experience with plasma exchange (PE) therapy in 13 patients with drug‐induced toxic epidermal necrolysis (TEN), 4 of whom had malignant disorders. Skin lesions covered 17% to 100% of total body surface area and 1 to 4 mucous membranes were involved. None of the patients was hospitalized in a burn unit. The patients underwent from 2 to 5 PE sessions (mean 3.4 ± 0.2 standard error of mean [SEM], median 3) exchanging 6.6 to 17.6 L of plasma (mean 10.1 ± 0.7 SEM, median 10). PE sessions were carried out every other day in 8 patients and daily in 5. Three patients died (23%) while the remaining 10 (77%) had a full recovery. Plasmapheresis may be an effective treatment in patients with drug‐induced TEN hospitalized outside a burn unit.