Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

Introduction

Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response.

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Peroxoniobium inhibits leukemia cell growth

A new class of polyoxoniobate complex has been synthesized and characterized as a novel anticancer agent for photodynamic therapy. The complex inhibits the growth of chronic myelogenous leukemia cells with an IC₅₀ value of 30 μM, in the dark. However, upon exposure to light (365 nm) there is a fivefold increase in the cytotoxic activity. Light radiation activate the complex with the formation of radical species capable of interacting with DNA according to our experimental and theoretical data.

A new class of polyoxoniobate complex has been synthesized and characterized as a novel anticancer agent for photodynamic therapy.

In this work, we prepared a photosensitive peroxoniobium complex presenting a balance with an active radical phase when illuminated with radiation of 365 nm. A versatile niobium species of amorphous structure was obtained by the reaction of niobium ammonium oxalate with ammonium hydroxide up to pH 7. The material obtained, a niobium oxyhydroxide (NbO₂(OH)) (white solid),^1,2 can be modified with the generation of NbO₂(OH)O₂˙⁻ peroxo groups (yellow solid).³ The yellow compound is formed by treatment with H₂O₂. The absorption radiation in the visible region due to the charge transfer transition between the peroxo group and the niobium is shown in Fig. 1.Open in a separate windowFig. 1UV-Vis profile of the catalysts.This complex with the radical as an intermediate is favored in the presence of visible and UV radiation. This property is of interest for photodynamic therapy of cancer (PDT), which involves the exposure of malignant cells containing a photosensitizer molecule to light irradiation, in the presence of oxygen species. The photoactivated drug produces reactive oxygen species that initiate a series of events, resulting in cell death. Selective light activation allows a preferential tumor destruction in comparison to healthy tissues.⁴ Several metal complexes exhibit photocytotoxicity under UV or visible light,^5,6 but data about niobium compounds are very scarce in the literature.⁷The polyoxoniobate, generated from niobium oxyhydroxide described here can be very active in the treatment of diseased cells when illuminated with visible or UV radiation due to its light absorption capacity because of the peroxo groups formed. The peroxoniobium complex has some advantages, such as ease synthesis and in mild conditions, high solubility, low activity under light off, and resistance to inactivation by thiol reagents. Moreover, it is nontoxic⁸ and does not employ noble metals like most of the compounds proposed in the literature. Actually, niobium oxide was tested as a bone implant component and showed absence of inflammatory cells or degeneration of the osteoblasts without any sign of damage to the preexisting bone tissue, showing compatibility with the bone tissue.^9–11The innovative part in the process of obtaining the polyoxoniobate complex presented in this work consists in the leaching of the complex when treating the niobium oxyhydroxide with H₂O₂. With the treatment, a yellow solid and a leached yellow liquid is obtained, which is the complex containing peroxoniobium in its structure, sensitive to the UV-Vis radiation generating radical species. This species generated with the leaching at neutral pH presents high negative charge and a kinetic volume of 223 nm. The XRD of the lyophilized polyoxoniobate indicated strong amorphous character. However, the polyoxoniobate is known to form well defined polyoxometalates such as Lindqvist ([Nb₆O₁₉]⁸⁻) and decaniobate ([Nb₁₀O₂₈]⁶⁻). Fig. 2 shows a comparison between the experimental and PBE/LANL2DZ/aug-cc-pVDZ DFT IR spectra. It is clear that the pattern of the decaniobate structure is closer to the experimental spectrum. One should keep in mind that DFT frequencies are normally 10% underestimated with respect to the experimental values. The broader absorption below 600 cm⁻¹ can be attributed to the interaction between different decaniobate structures forming the amorphous solid. The calculated peaks at 710, 760 and 860 cm⁻¹ are related to the experimental peaks of 800, 870 and 910 cm⁻¹ indicating that decaniobate is the local arrangement of the polyoxoniobate complex.Open in a separate windowFig. 2Infrared spectra for experimental procedures, Lindqvist and decaniobate structures (simulated). The line shape chosen was Lorentzian and the half-width is about 20.The generation of reactive oxygen under radiation was confirmed by the reaction of the complex with an organic dye, which was monitored by UV-Vis spectroscopy (Fig. 3). The spectrum of the dye solution shows the characteristic peak of the methylene blue (MB) at 663 nm (black trace). It can be clearly seen that in the presence of the peroxoniobium complex and radiation (365 nm) the signal decreased indicating the reaction of the peroxoniobium complex with the dye (blue trace). In the absence of light, there is no decrease in the signal related to the dye, indicating the need of the radiation to activate the oxidation action of the peroxoniobium complex. The equilibrium in which the radical species forms it is not necessary to use a photosensitizer agent, such as porphyrins.⁴ A further investigation was carried out by ³¹P NMR (Fig. S1^†) using guanosine as model molecule able to react with the peroxoniobium complex. The ³¹P NMR spectrum shown in Fig. S1-a^† corresponds to 5-GMP and revealed that the phosphorus atom in the structure exhibits a chemical shift at δ 5.93. When 5-GMP and the polyoxoniobate are in contact, no significant changes are observed in the ³¹P spectrum, only a small displacement of the phosphorus signal to δ 5.90 (Fig. S1-b^†). However, when the 5-GMP and polyoxoniobate mixture is submitted to radiation (Fig. S1-c^†), an interaction between the compounds occurs, giving rise to a new species that presents a different chemical shift in the P spectrum (δ 5.27).Open in a separate windowFig. 3UV-Vis profile of the reaction of the Nb complex with the organic dye (10 mg L⁻¹).The effect of the peroxoniobium on the growth of K562 cells was evaluated after 4 h of incubation. The compound inhibits K562 cell growth in a concentration-dependent manner, with an IC₅₀ of 30.0 ± 1.5 μmol L⁻¹. Ammonium niobate(v) oxalate was also tested and it has no effect on K562 cells up to 100 μM. The cytotoxic activity of polyoxoniobate increases by 5 times upon 5 min of UV-A light irradiation, with an IC₅₀ value of 6.2 ± 0.4 μmol L⁻¹ (Fig. 4). The higher activity, when exposed to light, associated to the low toxicity of niobium compounds place the peroxoniobium complex as a candidate for photodynamic therapy.Open in a separate windowFig. 4Photocytotoxic effect of the peroxoniobium complex. K562 cells were incubated for 4 h in the presence of different complex concentrations, in the dark (black bars) and after 5 min of UV-A light exposure (red bars). The values are the average of three independent experiments.There are few reports in the literature about the cytotoxic activity of niobium compounds. A peroxo niobium complex with ascorbic acid (K₃[Nb(Asc)(O₂)₃]) is moderately active in HL60 human leukemia cells but not in K562 human myelogenous leukemia cells.¹² A tetrameric Nb28-containing cluster inhibits the growth of the human breast cancer MCF-7 cells line with an IC₅₀ value of 5.21, after 48 h of incubation.¹³Methylene blue (MB) is one of the main photosensitizing agents used in PDT due to its good tissue penetration and low cytotoxicity.¹⁴ It is active in several types of tumors upon irradiation with red laser light.¹⁵ This fact allied to the ability of the peroxoniobium compound to interact with MB (Fig. 3) prompted us to investigate its effect in the MB photocytotoxicity. We have first checked that exposure to UV-A light did not affect the cytotoxicity of MB in K562 cells (

Short National Early Warning Score — Developing a Modified Early Warning Score

Introduction

Early Warning Score (EWS) systems have been developed for detecting hospital patients clinical deterioration. Many studies show that a National Early Warning Score (NEWS) performs well in discriminating survival from death in acute medical and surgical hospital wards. NEWS is validated for Portugal and is available for use. A simpler EWS system may help to reduce the risk of error, as well as increase clinician compliance with the tool.

Exercise training improves the IL-10/TNF-α cytokine balance in the gastrocnemius of rats with heart failure

Objective

This study examined the effects of exercise training (ExT) upon concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the gastrocnemius of rats with heart failure (HF) induced by left coronary artery ligation.

Can demographic and anthropometric characteristics predict clinical improvement in patients with chronic non-specific low back pain?

Objective

To identify potential prognostic factors that may predict clinical improvement of patients treated with different physical therapy interventions in the short-term.

Relationship of health literacy and adherence to oral anticoagulation therapy in patients with atrial fibrillation: a cross‐sectional study

Journal of Thrombosis and Thrombolysis - Oral anticoagulant therapy (OAT) has increased substantially due to the aging population and prevalence rise of atrial fibrillation (AF). Medication...     

Membrane and capillary blood components of diffusion capacity of the lung for carbon monoxide in pulmonary sarcoidosis: relation to exercise gas exchange

BACKGROUND: Resting pulmonary diffusing capacity of the lung for carbon monoxide (DLCO) is known to be the best predictor of arterial desaturation during exercise in patients with sarcoidosis. However, the relative contribution of each of the two components of DLCO-alveolar membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc)-remains unclear. STUDY OBJECTIVES: To evaluate which component is responsible for the decrease of resting DLCO in patients with sarcoidosis, and to determine which resting pulmonary function test, including Dm and Vc, is the best predictor of gas exchange abnormalities during submaximal exercise. DESIGN: Prospective analysis of patients referred to our department of respiratory medicine. PATIENTS: Twenty four patients with pulmonary sarcoidosis were separated into two groups according to chest radiographic findings: group 1, stages 2 and 3 (n = 15); group 2, stage 4 (n = 9). All the patients completed pulmonary function tests (flows, volumes, single-breath DLCO, transfer coefficient [Ka], Dm, Vc) and submaximal exercise (two steady-state levels of mild and moderate exercise corresponding respectively to a target oxygen consumption of approximately 10 to 15 mL/min/kg). RESULTS: DLCO was reduced in the two groups (group 1, 63 +/- 16% of predicted; group 2, 64 +/- 16% of predicted). Dm was severely decreased (group 1, 58 +/- 24% of predicted; group 2, 51 +/- 15% of predicted), whereas Vc was unchanged or only mildly decreased (group 1, 81 +/- 18% of predicted; group 2, 85 +/- 28% of predicted). Whatever the group of patients and the exercise level, Dm and DLCO were the strongest predictors (p < 0.001) of gas exchange abnormalities. Ka or volumes were weak predictors, and Vc or flows were not related with exercise gas exchange. CONCLUSIONS: This study demonstrates that a decrease in Dm mostly accounts for resting DLCO reduction, and that Dm as well as DLCO are highly predictive of gas exchange abnormalities at exercise in patients with sarcoidosis.     

Water-based resistance training program with isolated concentric action improves physical functional capacity and muscular strength in older women

Background

Resistance training has proven to be an excellent method for counteracting aging physical dysfunctions. However, its application in the liquid environment is not yet fully elucidated.

Aim

To investigate the effects of water-based resistance training (WBRT) with the concentric phase performed as fast as possible, compared to conventional resistance training (CRT), on physical functional capacity, muscle strength, and body composition in older women.

Methods

Thirteen healthy older women participated in the WBRT and 11 in the CRT. Estimation statistics focused on the effect size of the experiment/intervention were used. We also analyzed the intervention effect based on the percentage delta between WBRT and CRT.

Results

The WBRT group showed a negative large effect (d?=?? 0.922; p?=?0.0274) for the timed up and go, and a large effect for chair rise in 30″ and the elbow flex test (d?=?1.58; p?=?0.0012; d?=?2.8; p?=?0.01) respectively. Intervention comparisons based on the delta percentage between WBRT and CRT presented an intermediate effect (d?=?0.606; p?=?0.157) for the stair climb, a large effect (d?=?0.988; p?=?0.0282) for the timed up and go, and a large negative effect [d?=?? 1.32 (90.0% CI ? 1.92, ? 0.646); p?=?0.0038] for the elbow flex test. Concentric extensor-flexor peak torque (60°/s) showed an intermediate effect (d?=?0.749; p?=?0.0876; d?=?0.65; p?=?0.122 respectively). Body fat (%) demonstrated an intermediate effect (d?=?0.523; p?=?0.234).

Conclusion

WBRT with the concentric phase performed as fast as possible was able to improve physical functional capacity and maximal knee extension strength of older women.

     

Morphofunctional characteristics of the right ventricle in Chagas' dilated cardiomyopathy

Right ventricular involvement is a typical characteristic of Chagas' disease, and it has been described especially in the early stages of the disease. However, the role of right ventricular dysfunction in cardiac failure due to Chagas' cardiomyopathy has not been well established. Seventy-four patients with positive serology tests for Trypanosoma cruzi and Chagas' dilated cardiomyopathy characterized by left ventricular dilatation and systolic dysfunction were studied. Clinical history, physical exam, ECG, chest X-ray and Doppler echocardiogram with color flow mapping were obtained in all. Mean age was 47.5+/-12.9 and 51 were males (69%). Sixty-five patients (88%) were in NYHA functional classes I and II. Mild systolic dysfunction was present in 35 (47%) while in 18 (24%), dysfunction was moderate and in 21 (28%) it was severe. In 43 patients (58%), only the left ventricle was involved by echocardiographic criteria; the remaining 31 patients (42%) showed biventricular involvement. No patient had isolated involvement of the right ventricle. Greater dilation of the right ventricle was associated with larger diastolic (p<0.002) and systolic (p<0.001) diameters of the left ventricle. Systolic pulmonary artery pressure was obtained non-invasively in 54 patients. Pulmonary hypertension was associated with right ventricular dilation (p<0.005) and with systolic dysfunction of the left ventricle (p<0.001). In this group of patients with Chagas' dilated cardiomyopathy, right ventricular dysfunction was present when there was associated and significant involvement of the left ventricle and with higher levels of pulmonary pressure.