Assessing need for long-term oxygen therapy: a comparison of conventional evaluation and measures of ambulatory oximetry monitoring

BACKGROUND: Appropriate identification of hypoxic patients with chronic obstructive pulmonary disease (COPD) is important because of the demonstrated survival benefit of long-term oxygen therapy (LTOT) and its associated cost. Resting oxygen saturation (measured via pulse oximetry [S(pO2)]) and lowest exercise S(pO2) (during a 6-min walk test) is the standard method of determining LTOT requirements, but that method does not measure the patient's oxygenation during sleep or activities of daily living. We hypothesized that values obtained via the standard method would correlate poorly with values obtained via ambulatory oximetry monitoring. METHODS: We conducted a prospective, cohort study in an out-patient pulmonary clinic in a tertiary care referral center, with 20 stable COPD patients who were being evaluated for LTOT with conventional evaluation versus 16-24 hours of ambulatory oximetry. RESULTS: The resting S(pO2) did not correlate well with mean ambulatory S(pO2) (r = 0.64) or the percent of monitored time spent with S(pO2) < 88% (r = 0.49). The lowest exercise S(pO2) also did not predict mean ambulatory S(pO2) (r = 0.39) or the percent of monitored time spent with S(pO2) < 88% (r = 0.32). Conventional evaluation overestimated LTOT requirements with 16 of the 20 patients developing an S(pO2) < 88%, most of them with exercise only (ie, most had normal resting S(pO2)). With ambulatory monitoring, however, only 3 of the 16 patients spent > 10% of the monitored time with S(pO2) < 88%. CONCLUSION: There was a poor relationship between the conventional oxygenation assessment method and continuous ambulatory oximetry during LTOT screening with COPD patients.     

Serum antibody responses in Ethiopian meningitis patients infected with Neisseria meningitidis serogroup A sequence type 7

To elucidate critical components of protective immune responses induced during the natural course of serogroup A meningococcal disease, we studied acute-, early-convalescent-, and late-convalescent-phase sera from Ethiopian patients during outbreaks in 2002 to 2003. Sera were obtained from laboratory-confirmed patients positive for serogroup A sequence type 7 (ST-7) meningococci (A:4/21:P1.20,9) (n = 71) and from Ethiopian controls (n = 113). The sera were analyzed using an enzyme-linked immunosorbent assay to measure levels of immunoglobulin G (IgG) against serogroup A polysaccharide (APS) and outer membrane vesicles (OMVs) and for serum bactericidal activity (SBA) using both rabbit and human complement sources. Despite relatively high SBA titers and high levels of IgG against APS and OMVs in acute-phase patient sera, significant increases were seen in the early convalescent phase. Antibody concentrations returned to acute-phase levels in the late convalescent phase. Considering all patients' sera, a significant but low correlation (r = 0.46) was observed between SBA with rabbit complement (rSBA) using an ST-5 reference strain and SBA with human complement (hSBA) using an ST-7 strain from Ethiopia. While rSBA demonstrated a significant linear relation with IgG against APS, hSBA demonstrated significant linear relationships with IgG against both APS and OMV. This study indicates that antibodies against both outer membrane proteins and APS may be important in providing the protection induced during disease, as measured by hSBA. Therefore, outer membrane proteins could also have a role as components of future meningococcal vaccines for the African meningitis belt.     

Extent of allergic inflammation depends on intermittent versus continuous sensitization to house dust mite

Objective: House dust mite (HDM) exposure is used to model experimental asthma in mice. However, a direct comparison of inflammatory responses following continuous versus intermittent HDM exposure has not been reported. Therefore, we investigated whether the HDM dose at sensitization or challenge affects extent of inflammation in mice that were either continuously or intermittently sensitized with HDM.

Materials and methods: C57BL/6 mice received either 10 continuous exposures with 10?μg HDM per exposure or two intermittent HDM exposures over a period of two weeks and were subsequently challenged by three instillations with HDM during the third week. For the intermittent model, mice were sensitized with 1 or 10?μg HDM and challenged on three consecutive days with 1 or 10?μg HDM. Inflammatory cells in the bronchoalveolar lavage fluid and epithelial cell hyperplasia and mucous cell metaplasia were quantified.

Results: Significantly higher levels of inflammation and mucous cell metaplasia were observed when mice were sensitized intermittently compared with continuously. Intermittent sensitization and challenge with 10?μg HDM caused maximum inflammation, mucous cell metaplasia, and epithelial cell hyperplasia. However, sensitization with 1?μg HDM only also showed increased inflammation when challenged with 10?μg HDM.

Discussion: These findings suggest major differences in adaptive immunity, depending on the sensitization protocol.

Conclusions: Because of significant differences, the HDM sensitization protocol should be carefully considered when designing studies to investigate the underlying mechanisms of immunity in mouse models of asthma.     

Ovicidal and larvicidal activity of crude extracts of Maesa lanceolata and Plectranthus punctatus against Haemonchus contortus

The widespread development of anthelmintic resistance and high cost of the conventional anthelmintic drugs, has limited the control of gastrointestinal nematode parasites of sheep and goats and hence led to evaluation of medicinal plants as an alternative source of anthelmintics. In the current study, in vitro ovicidal and larvicidal activity of the leaves and fruits of the aqueous and hydro-alcoholic extracts of Maesa lanceolata and aerial parts of Plectranthus punctatus were evaluated on the egg and larvae of Haemonchus contortus using egg hatch assay and larval development test. All extracts of plants tested have shown complete inhibition of egg hatching at or below 1 mg/ml. ED₅₀ for egg hatch inhibition ranged from 0.11 to 0.29 mg/ml, for both the aqueous and hydro-alcoholic extracts of Plectranthus punctatus and Maesa lanceolata. All extracts have shown dose dependent inhibition of larval development with variable results. The complete inhibition (100%) at the maximum concentration tested (50 mg/ml) was obtained only for hydro-alcoholic extract of the fruits of Maesa lanceolata and the lowest inhibition (50.33%) was recorded for the hydro-alcoholic extract of the leaves of the same plant. The overall findings of the present study has shown that Plectranthus punctatus and Maesa lanceolata contain possible anthelmintic compounds and further evaluation of different extracts and fractions of these plants should be carried out.     

Cell penetrating peptides functionalized gambogic acid-nanostructured lipid carrier for cancer treatment

Tumor-targeted delivery is considered a crucial component of current anticancer drug development and is the best approach to increase the efficacy and reduce the toxicity. Nanomedicine, particularly ligand-based nanoparticles have shown a great potential for active targeting of tumor. Cell penetrating peptide is one of the promising ligands in a targeted cancer therapy. In this study, the gambogic acid-loaded nanostructured lipid carrier (GA-NLC) was modified with two kinds of cell penetrating peptides (cRGD and RGERPPR). The GA-NLC was prepared by emulsification and solvent evaporation method and coupled with cRGD, RGERPPR, and combination cRGD and RGERPPR to form GA-NLC-cRGD, GA-NLC-RGE, and GA-NLC-cRGD/RGE, respectively. The formulations were characterized by their particle size and morphology, zeta potential, encapsulation efficiency, and differential scanning calorimetry. In vitro cytotoxicity and cellular uptake study of the formulations were performed against breast cancer cell (MDA-MB-231). Furthermore, in vivo biodistribution and antitumor activity of the formulations were determined by in vivo imaging and in tumor-bearing nude mice, respectively. The result of in vitro cytotoxicity study showed that GA-NLC-RGE exhibited a significantly higher cytotoxicity on MDA-MB-231 as compared with GA-NLC and GA-Sol. Similarly, RGE-Cou-6-NLC showed remarkably higher uptake by the cells than other NLCs over the incubation period. The in vivo imaging study has demonstrated that among the formulations, the RGE-decorated DiR-NLC were more accumulated in the tumor site. The in vivo antitumor activity revealed that RGE-GA-NLC inhibits the tumor growth more efficiently than other formulations. In conclusion, RGERPPR has a potential as an effective carrier in targeting drug delivery of anticancer agents.     

Coinfection and clinical manifestations of tuberculosis in human immunodeficiency virus-infected and -uninfected adults at a teaching hospital, northwest Ethiopia.

BACKGROUND AND PURPOSE: The pattern of clinical presentations of tuberculosis (TB) is reflected in the microbiological, radiological, and histological characteristics of the disease. However, coinfection with human immunodeficiency virus (HIV) poses special diagnostic and therapeutic challenges. This study was aimed at assessing the clinical manifestations of TB in patients with or without HIV coinfection in a hospital-based cross-sectional study in Gondar, Ethiopia. METHODS: TB was diagnosed following standard clinical, bacteriological, radiological, and histological procedures. HIV serostatus was checked by enzyme-linked immunosorbent assay. RESULTS: This study included 257 TB patients, of whom 52.1% were coinfected with HIV. Pulmonary TB and extrapulmonary TB were diagnosed in 64.2% and 35.8% of the patients, respectively. No significant association was found between sputum smear positivity and HIV serostatus. One-fifth of the patients reported hemoptysis. More than one-third had chest pain, and >90% reported fever and weight loss. Night sweats and cough were reported by 86% and 82.5%, respectively. Coarse crepitations were the most frequent auscultatory finding (33.9%). Sputum smear positivity rate was 26.8%. Cavitation was significantly associated with sputum smear positivity (odds ratio = 9.0, 95% confidence interval = 2.4-34.1). Wasting, cough of 相似文献   

Maternal Death Review at a Tertiary Hospital in Ethiopia

BackgroundThere is conflicting data on the rate and trends of maternal mortality in Ethiopia. There is no previous study done on the magnitude and trends of maternal death at Saint Paul''s Hospital, an institution providing the largest labor and delivery services in Ethiopia. The objective of this study is to determine the magnitude, causes and contributing factors for maternal deaths in the institution.MethodsWe conducted a retrospective review of maternal deaths from January 2016 to December 2017. Data were analyzed using SPSS version 20.ResultsThe maternal mortality ratio of the institution was 228.3 per 100,000 live births. Direct maternal death accounted for 90% (n=36) of the deceased. The leading causes of the direct maternal deaths were hypertensive disorders of pregnancy (n=13, 32.5%), postpartum hemorrhage (n=10, 25%), sepsis (n=4, 10%), pulmonary thromboembolism (n=3, 7.5%) and amniotic fluid embolism (n=3, 7.5%).ConclusionThe maternal mortality ratio was lower than the ratios reported from other institutions in Ethiopia. Hypertensive disorders of pregnancy and malaria were the leading cause of direct and indirect causes of maternal deaths respectively. Embolism has become one of the top causes of maternal death in a rate like the developed nations. This might show the double burden of embolism and other causes of maternal mortality that developing countries might be facing.     

The role of Janus kinase 2 (JAK2) activation in pneumococcal EstA protein-induced inflammatory response in RAW 264.7 macrophages

In a previous study, we demonstrated pneumococcal EstA-induced inflammatory response through NF-κB and MAPK-dependent pathways. Herein, we tested the hypothesis that the Janus kinase 2 (JAK2) activation and associated signaling cascades may also be involved in EstA-induced inflammatory process in RAW 264.7 macrophages. Our immunoblot analysis indicated EstA-induced activation of JAK2, with the phosphorylated protein detected from 1 to 24 h post-stimulation. As type I interferon (IFN) signaling requires the JAK/STAT pathway, we investigated EstA-induced expression of INF-α4 and INF-β by semi-quantitative and quantitative RT PCR. Our results indicated both concentration- and time-dependent increases in both IFN-α4 and IFN-β mRNA expression after EstA challenge, with the highest fold-increases observed at 4 h and 6 h post-stimulation for IFN-α4 and IFN-β mRNA, respectively. Furthermore, we applied a pharmacological approach to demonstrate the effect of JAK2 inhibition on EstA-induced nitric oxide (NO) and pro-inflammatory cytokine production. The JAK2 inhibitor AG-490 reduced significantly (P < 0.05) EstA-induced NO production and the expression of iNOS mRNA in a concentration-dependent manner. Similarly, EstA-induced IL-1β and IL-6 production and their respective mRNA expression were markedly suppressed by AG-490. However, AG-490 had no inhibitory effect on both mRNA and protein levels of TNF-α. Taken together, we demonstrate that JAK2 activation and IFN I signaling are integral parts of EstA-induced inflammatory process. Further studies will elucidate the interaction of the different signaling pathways, the specific downstream targets of JAK2, the kinetics of cytokine release, and if EstA could induce the pro-inflammatory mediators to the same extent in alveolar macrophages.