Efficacy of salbutamol by nebulizer versus metered dose inhaler with home-made non-valved spacer in acute exacerbation of childhood asthma

This study was done to evaluate and to compare the efficacy of jet nebulizer and metered dose inhaler (MDI) with home-made non-valved spacer (HM NVS) to deliver aerosolized salbutamol in acute exacerbation of asthma in children. HM NVS was made by 500ml plastic mineral water bottle. It was perforated at the bottom for the insertion of MDI and proximal end was cut for placing the mouth. This prospective randomized study was conducted in the department of Pediatrics, Dhaka Medical College Hospital, during April 2007 to March 2008 with 50 known cases (2-12 years) of bronchial asthma with acute exacerbation. After randomized enrollment, each patient received three doses of salbutamol either through a jet nebulizer or through a HM NVS. Oxygen saturation (SaO2), wheeze, heart rate, respiratory rate were recorded throughout the treatment period. Data were analyzed with SPSS for Windows 10.0 at p value <0.05 was considered significant. The mean age of patients was 59.8 months in nebulizer group versus 69.4 months in MDI with HM NVS group. Baseline clinical characteristics in nebulizer group were SaO2 87.7±2.5 versus 89.0±1.8 percent, RR 59.2±7.3 vs. 63.2±4.8 per minute, HR 155.4±11.8 versus 149.0±10.8 per minute and wheeze in 22(88.0%) cases versus 21(84.0%) cases respectively (p>0.05). After therapy improvement was noted among the nebulizer group (SaO2 87.7±2.5 vs. 94.3±2.8 percent; RR 59.2±7.3 vs. 39.3±4.9 per minute; HR 155.4±11.8 vs. 151.60±17.3 per minute; wheeze 88% vs. 8%) as well as in the MDI with HM NVS group (SaO2 89.0±1.8 vs. 94.8±1.8 percent; RR 63.2±4.8 vs. 38.7±6.4 per minute; HR 149.0±10.8 vs. 144.5±13.5 per minute; wheeze 84% vs. 16%) [p<0.001; CI:95%]. However, these improvements did not differ significantly between the nebulizer group and HM NVS group (SaO2 94.3±2.8 vs. 94.8±1.8 percent, RR 39.3±4.9 vs. 38.7±6.4 per minute, HR 151.60±17.3 vs. 144.5±13.5 per minute and wheeze persisted in 2(8.0%) cases versus 4(16.0%) cases respectively) [p>0.05]. The overall response to these modalities of treatment was satisfactory in nebulizer (19/25) and HM NVS (17/25). Salbutamol delivered through both nebulizer as well as MDI with HM NVS is equally effective in the treatment of acute asthma in children.     

Attention does more than modulate suppressive interactions: attending to multiple items

Directing attention to a visual item enhances its representations, making it more likely to guide behavior (Corbetta et al. 1991). Attention is thought to produce this enhancement by biasing suppressive interactions among multiple items in visual cortex in favor of the attended item (e.g., Desimone and Duncan 1995; Reynolds and Heeger 2009). We ask whether target enhancement and modulation of suppressive interactions are in fact inextricably linked or whether they can be decoupled. In particular, we ask whether simultaneously directing attention to multiple items may be one means of dissociating the influence of attention-related enhancement from the effects of inter-item suppression. When multiple items are attended, suppressive interactions in visual cortex limit the effectiveness with which attention may act on their representations, presumably because “biasing” the interactions in favor of a single item is no longer possible (Scalf and Beck 2010). In this experiment, we directly investigate whether applying attention to multiple competing stimulus items has any influence on either their evoked signal or their suppressive interactions. Both BOLD signal evoked by the items in V4 and behavioral responses to those items were significantly compromised by simultaneous presentation relative to simultaneous presentation, indicating that when the items appeared at the same time, they interacted in a mutually suppressive manner that compromised their ability to guide behavior. Attention significantly enhanced signal in V4. The attentional status of the items, however, had no influence on the suppressive effects of simultaneous presentation. To our knowledge, these data are the first to explicitly decouple the effects of top-down attention from those of inter-item suppression.     

Identification of self-replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression

Discrimination of neural stem cells from other progenitors in the developing mammalian brain has been hampered by the lack of specific markers. Identifying the progenitor pools and signalling pathways that guide mammalian neurogenesis are central to understanding the complex mechanisms that govern development of the nervous system. Notch signalling plays a pivotal role in the development of the mammalian nervous system by maintaining multipotent neural stem cells and regulating their fate. In order to identify putative neural stem cells in situ, we generated transgenic mice that express Green Fluorescent Protein (GFP) and report Notch signalling activity in the developing CNS. Here we show the subdivision of progenitors within the neural tube of these mice. We purify progenitors from the neural tube and show that cells with the highest levels of Notch-reporter activity have self-renewal capability and multipotency, whereas those lacking Hes5 expression do not form neurospheres in vitro. Using marker protein co-expression and cell sorting, we show that both neuroepithelial cells as well as some radial glia at all axial levels of the embryonic neural tube display active Notch signalling. However, Tbr2-positive basal progenitors of the developing telencephalon and differentiating Islet1/2- and Lim1-positive motor neurons outside the ventricular zone do not express Hes5-GFP. Quantitative analysis showed that Hes5 expression correlates better with neural stem cell potential than expression of the related gene Hes1. Thus, Notch activity through Hes5 identifies multipotent progenitors with stem cell properties and subdivides the different progenitors into defined pools.     

The molecular pathology of beta-thalassemia in Turkey: the Boğaziçi university experience

The thalassemias are a diverse group of hemoglobin (Hb) disorders characterized by a reduced synthesis of the globin chains of Hb. Today, more than 200 mutations, affecting different levels of beta-globin gene expression, by a variety of mechanisms, are known to result in a beta-thalassemia (thal) phenotype. According to recent findings, the multilayered complexity in the phenotype of beta-thal is the result not only of marked molecular heterogeneity at the beta-globin locus, but at the level of several other genes as well. The heterogeneity at the beta-globin locus, which is the most reliable and predictive factor of disease phenotype, is simplified, to a certain extent, by the fact that the mutations are ethnic-group specific. Fifty out of >200 beta-thal mutations account for 90-95% beta-thalassemias worldwide. In the broad group of Mediterranean countries, approximately 35 mutations have been reported thus far; however, allele frequencies vary among countries. beta-Thal is a major public health concern in Turkey; throughout the country the gene frequency is estimated to be 2.1%, but in certain regions, this figure increases to 10%. The estimated number of carriers is 1,300,000 and the number of homozygous beta-thal patients is around 4,000. The number of affected births is higher than expected, since the birthrate is still very high in Turkey, and the number of consanguineous marriages is above 60% in the eastern parts of the country. Unlike many other Mediterranean countries, beta-thal in Turkey is very heterogeneous at the clinical level, transfusion-dependent beta-thal major predominating. Between 1987 and 2006, more than 1,500 patients with homozyous beta-thal, unrelated and not preselected, were investigated by DNA analysis. Our results revealed that by far the most common mutation in Turkey is IVS-I-110 (G-->A), followed by IVS-I-6 (T-->C) and frameshift codon (FSC) 8 (-AA). The six most common mutations add up to approximately 70.3%, and the overall frequency of the first 12 mutations is 83.3%. The ratio of beta (0):beta (+)-thal mutations is 1:1, but the majority of beta (+)-thal cases carry the severe IVS-I-110 lesion; thus, most of these mutations give rise to beta-thal major in homozygous or compound heterozygous combinations. In addition to the 12 common mutations, several rare and four novel beta-thal mutations were reported in the framework of this project, totaling 36 mutations. Turkey's large molecular heterogeneity can be explained by its unique geographical position and rich history, an important crossroad between cultures, civilizations and continents for several centuries. This study shows that despite its great molecular heterogeneity, and with the advent of polymerase chain reaction (PCR)-based techniques and improved methods of early fetal sampling, heterozygote screening and prenatal diagnosis are feasible in Turkey.     

Do different delivery systems of hormone therapy have different effects on psychological symptoms in surgically menopausal women? A randomized controlled trial

Objective

To compare the influence of different delivery forms of estrogen therapy on menopausal and psychological symptoms in surgically menopausal women.

Study design

Surgically menopausal women were assigned to a 1-year-therapy with oral conjugated estrogen 0.625 mg/day (n = 35), intranasal 300 μg/day estradiol hemihidrate (n = 33), percutaneous gel 1.5 mg/day estradiol hemihidrate (n = 32) or no treatment (control group, n = 32). Serum E₂ and FSH levels, Kupperman's Scale used to assess climacteric symptoms, Hamilton Depression Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) scores were assessed before and after 1-year-therapy.

Results

After 1 year, the greatest increase in E₂ was in the oral group, followed by the transdermal gel, and then the intranasal group (oral vs transdermal gel: p = 0.022: oral vs intranasal: p = 0.0001; transdermal gel vs intranasal: p = 0.0001). All treatment groups improved significantly in total Kupperman index score and HARS (p < 0.05) with no difference between the groups. With regard to HDRS, all treatment groups improved significantly (p < 0.05) with the greatest improvement in the oral group, and no difference between transdermal gel and intranasal groups (oral vs transdermal gel: p = 0.015; oral vs intranasal: p = 0.001; transdermal gel vs intranasal: p = 0.735). Control group scored worse in all tests after study (p < 0.05). All scores correlated significantly with post-treatment serum E₂ and FSH levels (p < 0.001).

Conclusion

Oral, intranasal and percutaneous gel estradiol therapies significantly improve menopausal and psychological symptoms in surgically menopausal women with oral route better than transdermal gel and intranasal modalities against depressive mood.     

Effect of butylated hydroxytoluene (E321) pretreatment versus L-arginine on liver injury after sub-lethal dose of endotoxin administration

Aim of this study was to compare the effects of L-arginine (L-arg) and food-antioxidant butylated hydroxytoluene (BHT) against oxidative stress of Escherichia coli endotoxin (LPS) in liver. Ninety Wistar albino rats were assigned in three groups. Rats received one of the following pre-treatment previous to 5mg/kg LPS intraperitoneally: saline, L-arg (NO donor, 100mg/kg) or BHT (250 mg/kg/day), for 3 days. At second, fourth and sixth hours, plasma nitrite-plus-nitrate, circulating liver enzymes, glutathione levels, superoxide dismutase, glutathione peroxidase activities were measured. The most remarkable liver injury was evident in BHT pre-treated animals at all time points compared to L-arg pre-treated rats. While BHT enhanced superoxide dismutase activities following LPS, glutathione decreased simultaneously compared to L-arg group. Although the risk associated with the use of BHT alone in subthreshold doses appeared to be low, higher risk of liver toxicity should be considered when over-consuming this food additive in endotoxemic settings.     

The role of PET-CT in the differential diagnosis of thymic mass after treatment of patients with lymphoma

Thymic hyperplasia is a common phenomenon in both children and young adults after chemotherapy and may explain the finding of a mediastinal mass in patients with malignant lymphoma after complete remission. In the present study, we report 5 cases with malignant lymphoma presenting with a mediastinal mass on CT scan after completion of chemotherapy diagnosed as thymic hyperplasia by PET-CT imaging. We retrospectively analyzed 5 patients who presented with anterior mediastinal masses a median of 4 months (range 3–6) after achieving complete remission following successful treatment for malignant lymphoma. Three patients were diagnosed with Hodgkin’s lymphoma (HL) and the others with non-Hodgkin’s lymphoma (NHL). The median age of the patients was 23 (range of 18–47). PET-CT was performed on these patients to determine the characteristics of a mass which had been detected on CT. PET-CT was performed for all patients, and the thymic masses demonstrated only mild FDG uptake considered to be consistent with thymic hyperplasia. During a median of 24 months of follow-up, all patients were recurrence-free with a median survival of 15 months (range 10–26 months). It is important to be aware of the possibility of thymic hyperplasia after chemotherapy to avoid misdiagnosis or over-staging of disease, as well as unnecessary biopsies, especially when the presenting anterior mediastinal mass was originally located near the thymus on CT scan. Mild FDG PET uptake was sufficient for the diagnosis of benign disease in the cases in this study.     

Lidocaine for prevention of propofol injection-induced pain: A prospective, randomized, double-blind, controlled study of the effect of duration of venous occlusion with a tourniquet in adults

Background: Many patients experience pain on injection of propofol. The use of lidocaine to prevent propofol injection pain is common. The analgesic effect of pre-injected lidocaine has been found to increase when a tourniquet is used.Objective: The aim of this study was to compare the effectiveness of various venous occlusion times with lidocaine analgesia to prevent pain during propofol injection.Methods: In this prospective, randomized, double-blind, controlled study, women aged 18 to 45 years, classifed as American Society of Anesthesiologists physical sta- tus I or II, who were scheduled to undergo elective surgery under general anesthesia induced with propofol, were randomly assigned to 1 of 5 groups: group 1, 2% lidocaine 20 mg in saline in a total volume of 10 mL and no venous occlusion; group 2, 2% lidocaine 20 mg in saline in a total volume of 10 mL plus venous occlusion for 15 seconds; group 3, 2% lidocaine plus venous occlusion for 30 seconds; group 4, 2% lidocaine plus venous occlusion for 60 seconds; and group 5, saline 10 mL and no venous occlusion. When the first 25% of the calculated propofol dose was administered, patients were asked about propofol-induced pain using a verbal pain scale (0 = no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain). All patients and the anesthesiologist who evaluated pain severity were blinded to the study preparation being used.Results: The study comprised 100 women who were randomly divided into 5 groups of 20 patients each. Significantly more patients in group 5 (18 [90%] patients; P < 0.05) reported pain compared with the other treatment groups. In groups 2, 3, and 4, in which venous occlusion was applied, pain was reported during propofol injection in 6 (30%), 7 (35%), and 2 (10%) patients, respectively. The incidence of reported pain was significantly greater in group 1 (lidocaine without venous occlusion) than in group 4 (P < 0.05); however, the incidence of pain was similar in group 1 compared with groups 2 and 3.Conclusions: The present study found that pretreatment with lidocaine 20 mg with or without venous occlusion significantly reduced the incidence and the severity of pain during the injection of propofol when compared with the group with no venous occlusion administered saline. In addition, pretreatment with lidocaine 20 mg plus venous occlusion for 60 seconds significantly reduced the incidence of propofol-induced pain compared with lidocaine without venous occlusion.     

Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells

The proprotein convertases (PCs) are implicated in the activation of various precursor proteins that play an important role in tumor cell metastasis. Here, we report their involvement in the regulation of the metastatic potential of colorectal tumor cells. PC function in the human and murine colon carcinoma cell lines HT-29 and CT-26, respectively, was inhibited using siRNA targeting the PCs furin, PACE4, PC5, and PC7 or by overexpression of the general PC inhibitor alpha1-antitrypsin Portland (alpha1-PDX). We found that overexpression of alpha1-PDX and knockdown of furin expression inhibited processing of IGF-1 receptor and its subsequent activation by IGF-1 to induce IRS-1 and Akt phosphorylation, all important in colon carcinoma metastasis. These data suggest that the PC furin is a major IGF-1 receptor convertase. Expression of alpha1-PDX reduced the production of TNF-alpha and IL-1alpha by human colon carcinoma cells, and incubation of murine liver endothelial cells with conditioned media derived from these cells failed to induce tumor cell adhesion to activated murine endothelial cells, a critical step in metastatic invasion. Furthermore, colon carcinoma cells in which PC activity was inhibited by overexpression of alpha1-PDX when injected into the portal vein of mice showed a significantly reduced ability to form liver metastases. This suggests that inhibition of PCs is a potentially promising strategy for the prevention of colorectal liver metastasis.