Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs

BACKGROUND: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system. STUDY DESIGN AND METHODS: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an intraoperative volume-compensated blood loss was simulated. The efficacy of three therapeutic regimens in maintaining tissue oxygenation was compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of autologous RBCs; 2) PFC group (n = 7): bolus application of a second-generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and tissue oxygenation were assessed. RESULTS: Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood loss. In the PFC and control groups, heart rate and cardiac index increased significantly in response to further ANH. Tissue oxygenation was not different in the PFC and the RBC groups. Direct comparison of the PFC and control groups revealed better tissue oxygenation in the PFC group, as reflected by significantly higher mixed venous, coronary venous, and local tissue pO2 on liver and skeletal muscle. CONCLUSION: Bolus intravenous administration of 60- percent (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to one of 3 g per dL were as effective as autologous RBC transfusion in maintaining tissue oxygenation during volume-compensated blood loss designed to mimic surgical bleeding.     

The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors

The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort 7to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong antiproliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G(1)/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both eukaryotic translation initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with 2 main proproliferative signaling pathways, that is, the AKT and the MEK/extracellular signal-regulated kinase pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong antitumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET.     

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia

Objective

To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia.

Methods

We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence.

Findings

There were 526 pneumonia events among 10 600 children – an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses.

Conclusion

There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.     

诺卡式菌性角膜炎表现为盘状角膜炎1例

目的:报告诺卡式菌属感染引起的盘状角膜炎病例1例。方法:病例报告。结果:患者,男,13岁,无角膜接触镜使用史,在小溪里游泳后,右眼疼痛伴视力下降2wk。最佳矫正视力:右眼6/30(0.2)。检查发现角膜基质存在形态规则的旁中心盘状浸润伴炎症反应。角膜敏感度下降。最初角膜刮片镜检行革兰氏染色阴性,棘阿米巴角膜刮片和培养阴性。诊断为病毒性盘状角膜炎,给予口服阿昔洛韦和局部使用激素眼药水。2wk后患者视力恶化伴角膜损伤加重,再次角膜取材刮片行革兰氏染色提示诺卡式菌属感染,按经验局部给予3g/L加替沙星眼药水后,临床效果明显。治疗6mo后,视力达到6/6仅在角膜中心留有少量角膜混浊。结论:诺卡式菌属感染延误诊断可以导致病情恶化。如果采用正确的治疗,诺卡式菌属感染引起的角膜炎可以恢复良好,仅留少量瘢痕,获得较好的视力。     

Hematopoietic cell activation in the subventricular zone after Theiler's virus infection

Background

The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis.

Method

Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes.

Results

Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex.

Conclusion

The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form.     

Acute spinal cord injury: MR imaging at 1.5 T

Thirty-seven magnetic resonance (MR) imaging studies were performed with a 1.5-T magnet and surface coils in 27 patients with suspected spinal cord injuries. Imaging was performed 1 day to 6 weeks after injury. Cord abnormalities were seen with MR in 19 patients, while skeletal and/or ligamentous injuries were seen in 21 (78%). Three types of MR signal patterns were seen in association with cord injuries. Acute intraspinal hemorrhage was seen in five patients with cord injuries and demonstrated decreased signal intensity on T2-weighted images obtained within 24 hours of injury. Cord edema and contusion had high signal intensity on T2-weighted images and were observed in 12 cases with cord injury. Neurologic recovery, determined in 16 patients, was insignificant in patients with intraspinal hemorrhage; however, patients with cord edema or contusion recovered significant neurologic function. MR at 1.5 T is extremely useful in the diagnosis of acute cord injury and also demonstrates potential in predicting neurologic recovery.     

Dental caries risk indicators among Australian Aboriginal young adults

Jamieson LM, Roberts‐Thomson KF, Sayers SM. Dental caries risk indicators among Australian Aboriginal young adults. Community Dent Oral Epidemiol 2010; 38: 213–221. © 2009 John Wiley & Sons A/S Abstract – Objectives: To determine dental caries risk indicators among a birth cohort of Australian Aboriginal young adults (n = 442). Methods: Data were from the Aboriginal Birth Cohort study, a prospective longitudinal investigation of Aboriginal individuals born 1987–1990 at an Australian regional hospital. Models representing demographic, socioeconomic, behavioural, dental service utilization and clinical oral health variables were tested using multivariate regression. Results: The percent DT > 0 was 72.9 (95% CI 68.7–77.1), mean DT was 4.19 (95% CI 3.8–4.6), percent DMFT > 0 was 77.4 (95% CI 73.5–81.3) and mean DMFT was 4.84 (95% CI 4.4–5.3). After controlling for other covariates, risk indicators for percent DT > 0 included soft drink consumption every day or a few times a week (PR 1.25, 95% CI 1.08–1.45), not consuming milk every day or a few times a week (PR 1.16, 95% CI 1.04–1.30) and sweet consumption every day or a few times a week (PR 1.18, 95% CI 1.04–1.33). Risk indicators for mean DT included sweet consumption every day or a few times a week (B = 1.14, 95% CI 0.27–2.02), nonownership of a toothbrush (B = 0.91, 95% CI 0.10–1.87) and presence of plaque (B = 2.46, 95% CI 0.96–3.96). Those with 4 + occupants in their house the previous night had 1.2 times the prevalence of having DMFT > 0 than their counterparts with less household occupants (95% CI 1.01–1.49). Percent DMFT > 0 was also associated with consumption of soft drink every day or a few times a week (PR 1.18, 95% CI 1.04–1.34) and consumption of sweets every day or a few times a week (PR 1.23, 95% CI 1.10–1.37). Mean DMFT was higher among those who consumed sweets every day or a few times a week (B = 0.13, 95% CI 0.05–0.22) and who had dental anxiety (B = 0.10, 95% CI 0.01–0.19). Conclusions: In an Australian Aboriginal young adult cohort, risk indicators for dental caries included social determinants such as household size, dietary behaviours such as regular consumption of soft drink and sweets, dental behaviour such as nonownership of a toothbrush and dental anxiety.