Prediction and Detection of Secondary Hemorrhages after Thrombolytic Therapy in Ischemic Stroke

Abstract It is well established that thrombolytic therapy increases the risk of secondary intracerebral hemorrhage in ischemic stroke patients. However, the term “intracerebral hemorrhage” (ICH) covers a wide spectrum from tiny spots of blood to massive space-occupying hematoma. We will review the etiology and clinical consequences of secondary hemorrhage after thrombolysis in ischemic stroke patients and discuss the ability of magnetic resonance imaging (MRI) to predict this phenomenon. MRI is a highly sensitive tool for detection of hemorrhagic transformation after ischemic stroke. The definitions of a so-called symptomatic hemorrhage after ischemic infarction differ considerably and will also be described. Attributing a causal relationship of a clinical deterioration to a secondary hemorrhage is not easy and should be only addressed when it exceeds at least 30% of the infarct volume. In other patients, secondary hemorrhage might be regarded as side effect of reperfusion within the region with the most severe perfusion deficit. Cerebral microbleeds (CMBs) are a frequent finding in patients with leukoaraiosis and appear to be a general marker of various types of bleeding- prone small vessel disease and a predictor of recurrent vascular events. Current data do not support the hypothesis that the detection of CMBs is a useful diagnostic criterion for the exclusion of patients with CMBs from thrombolytic therapy. However, an increased risk for the rare patients with numerous CMBs can not be ruled out.      

Not enough there, too many here: understanding geographical imbalances in the distribution of the health workforce

Access to good-quality health services is crucial for the improvement of many health outcomes, such as those targeted by the Millennium Development Goals (MDGs) adopted by the international community in 2000. The health-related MDGs cannot be achieved if vulnerable populations do not have access to skilled personnel and to other necessary inputs. This paper focuses on the geographical dimension of access and on one of its critical determinants: the availability of qualified personnel. The objective of this paper is to offer a better understanding of the determinants of geographical imbalances in the distribution of health personnel, and to identify and assess the strategies developed to correct them. It reviews the recent literature on determinants, barriers and the effects of strategies that attempted to correct geographical imbalances, with a focus on empirical studies from developing and developed countries. An analysis of determinants of success and failures of strategies implemented, and a summary of lessons learnt, is included.     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.     

Subclinical course of adult visceral Niemann–Pick type C1 disease. A rare or underdiagnosed disorder?

Summary  We present the third case of Niemann–Pick disease type C without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann–Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of Niemann–Pick disease type C (NPC). To verify the histopathological findings, SMPD1, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2 gene. The pathogenicity of both NPC1 variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of Niemann–Pick disease type C, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. Electronic supplementary material  Supplementary material is available for this article at     

神经病、神经外科和精神病学杂志

严重脑损伤后17年的社会心理调整;由琥珀酸脱氢酶（SDHA）黄素蛋白（Fp）亚单位突变所致Leigh综合征;动脉瘤性蛛网膜下腔出血早期循环中的内皮细胞激活标记物水平：与脑缺血事件和预后的关系;CSF前列腺素E2水平与认知功能下降和阿尔茨海默病存活率的关系；变异型克罗伊茨费尔特-雅各布病患者的CSF磷酸-tau蛋白浓度升高：诊断和病理学意义。     

Pulmonary Lophomonas blattarum infection in patients with kidney allograft transplantation

The aim of the study was to analyse the clinical manifestation and management of pulmonary Lophomonas blattarum infection in four allograft transplantation recipients retrospectively. Four patients with pulmonary L. blattarum infection were diagnosed by using Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) examination. Their clinical manifestation and management are summarized. Four cases of pulmonary L. blattarum were found during the period from the second month to the third month after transplantation. Concurring infection by other pathogens was found in three of them. Common initial symptoms included fever (>38 degrees C) without cough and breathlessness. Lower lobe shadowing could be found on chest X-ray. Body temperature decreased to the normal range in three patients and to 37.5 degrees C in the other one, after intravenous injection of metronidazole and tapering immunosuppressant. Radiological examination confirmed improved health condition of the patients afterwards. Two patients received repeated FOB and only dead L. blattarum was found. Pulmonary L. blattarum infection in allograft transplant recipients carry relatively obscure initial symptoms. Possible L. blattarum infection needs to be screened in post-transplantation pulmonary infection patients with similar symptoms, especially in those who respond poorly to anti-infection treatment. Microscopic examination of BAL fluid can help to identify pulmonary L. blattarum infection and metronidazole is an ideal treatment choice.