Delayed Administration of the K+ Channel Activator Cromakalim Attenuates Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage

Summary ? Background. Delayed cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage (SAH). Recent evidence indicates that the potassium channel activator cromakalim is capable of limiting cerebral vasospasm in rabbits when administered immediately after experimental SAH (i.e. before spastic constriction has been initiated). However, the ultimate clinical value of cromakalim for treating vasospasm will depend in part on its effectiveness when administered after SAH-induced constriction has already been initiated. The present study examined the effects of cromakalim on vasospasm when treatment was initiated after SAH-induced constriction was underway.  Methods. New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. Cromakalim (0.03, 0.1 or 0.3 mg/kg) or vehicle was injected intravenously at 8 hour intervals beginning 24 hours post-SAH. Animals were killed by perfusion fixation 48 hours after SAH. Basilar arteries were removed and sectioned, and cross-sectional area was measured.  Findings. The average cross sectional areas of basilar arteries were reduced by 64% and 68% in the SAH-only and SAH+vehicle groups, respectively. Treatment with cromakalim dose-dependently attenuated SAH-induced constriction. The groups treated with 0.03, 0.1, and 0.3 mg/kg cromakalim exhibited average decreases in cross-sectional area of 57%, 42%, and 19%, respectively.  Interpretation. These findings indicate that cromakalim dose-dependently attenuates cerebral vasospasm when administered 24 hours after experimental SAH in the rabbit. The results suggest K_ATP channel activators, such as cromakalim, could be of benefit for reversing cerebral vasospasm after aneurysmal SAH.     

Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping

OBJECT: Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of the central nervous system are malignant, invasive embryonal tumors with predominantly neuronal differentiation that comprise 20% of pediatric brain tumors. Cytogenetic analysis has shown that alterations in chromosome 17, particularly the loss of 17p and the formation of isochromosome 17q, as well as the gain of chromosome 7 are the most common changes among this group of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel regions of gain, loss, and amplification. The advent of more sophisticated multicolored fluorescence in situ hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits complete recognition of all aberrations including extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinations of classic banding analysis, FISH, CGH, and SKY to examine comprehensively the chromosomal aberrations present in this tumor group and to attempt to identify common structural rearrangement(s). METHODS: The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the tumors studied, which confirms data reported in the current literature. However, the authors have also combined the results of all three molecular cytogenetic assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal rearrangement (gained, lost, or involved in structural rearrangement). CONCLUSIONS: The combined results indicate that chromosomes 7 and 17 are the most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, followed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identified in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally, desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher karyotype heterogeneity, amplification, and aneusomy than classic medulloblastomas.     

Overview of current standpoints in profiling of circulating tumor cells

The goal of this review is summarizing current technologies developed as the in vitro prognostic/diagnostic systems that can rapidly separate and detect circulating tumor cells (CTCs) from cancer patient’s blood (1–10 CTCs of 1 billion red blood cells) by labeled and non-labeled method. The review is focused on three major areas of CTC research (1) Summary of previous research on capturing of CTCs, (2) New development of the in vitro prognostic diagnosis system of cancer that is capable of rapid separation of CTCs, (3) Future direction on development of new technologies for CTC profiling. Current CTC researches have helped on identifying patients who may benefit from chemotherapy before treatment, patients who may benefit from continued chemotherapy, and leading to clinical development of CTC-guided chemotherapy strategies. We analyze the feasibility of clinical application of these current CTC research for the ultimate goal of increasing the survivability of cancer patient. The biomolecular assays of viable CTCs from cancer patient may elucidate the mechanism of metastasis and tumor initiating cells and also may have high impact on the development of personalized medicine to overcome the incurable diseases.     

A pure fluid-filled intradural cyst associated with intradural disc herniation and possible pathogenesis: a case report

Background contextLumbar intradural disc herniation (IDH) is rare, and intradural cyst associated with IDH is quite rare. Only seven cases of an intradural cyst associated with lumbar disc herniation have been reported, and all were gas-filled cysts. We report the first case, to our knowledge, of a fluid-filled intradural cyst associated with IDH.PurposeTo report an extremely rare case of a fluid-filled intradural cyst associated with lumbar IDH and suggests the possible pathogenesis.Study designCase report.MethodsAn 82-year-old woman presented with right leg pain and motor weakness. Computed tomography and magnetic resonance imaging (MRI) scans showed calcified lumbar disc herniation and an intradural cystic mass at the L1–L2 level. An MRI, which was performed 2 years before admission, showed an IDH without a cyst at the same level.ResultsSurgical resection of the intradural cyst was performed. Intraoperative finding showed a fluid-filled intradural cyst with 1-cm diameter of displacing nerve rootlets. The cyst was connected with extradural cystic components through a ventral dural hole, but the tract was blocked by fibrous septum. Histopathologic examination showed a pseudocyst that consisted of degenerative cartilaginous and fibrous tissues, including degenerative disc materials. We concluded that the cyst was an intradural cyst transformed from the intradural disc fragment.ConclusionsThe current case is the first report to our knowlege of a fluid-filled intradural cyst associated with IDH. The possible mechanism may be focal degeneration and spontaneous absorption of the intradural disc with fluid production. Unlike the gas-filled intradural cysts, the cause of the pure fluid-filled cyst may be disconnection from the intervertebral vacuum because of a calcified disc and septation of the cyst.     

Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Shear Wave Elastography: A Review on the Confounding Factors and Their Potential Mitigation in Detecting Chronic Kidney Disease

Early detection of chronic kidney disease is important to prevent progression of irreversible kidney damage, reducing the need for renal transplantation. Shear wave elastography is ideal as a quantitative imaging modality to detect chronic kidney disease because of its non-invasive nature, low cost and portability, making it highly accessible. However, the complexity of the kidney architecture and its tissue properties give rise to various confounding factors that affect the reliability of shear wave elastography in detecting chronic kidney disease, thus limiting its application to clinical trials. The objective of this review is to highlight the confounding factors presented by the complex properties of the kidney, in addition to outlining potential mitigation strategies, along with the prospect of increasing the versatility and reliability of shear wave elastography in detecting chronic kidney disease.     

Predictors of HIV Testing and Their Influence on PrEP Acceptance in Men Who Have Sex with Men: A Cross-Sectional Study

HIV testing is the gateway to biomedical means of prevention and treatment. Identifying predictors of HIV testing is important to inform future preventive interventions. Of 444 men who have sex with men without known HIV infection enrolled in a study in Hong Kong, 64% had ever been HIV-tested. Testers were generally older, better educated, had a higher monthly income, and more likely self-identified as gay. Testers often used Internet and frequented saunas for sex networking, compared with non-testers attending bars, massage centres and public toilets. HIV testing habit also varied with the profile of body image type and preferred type in sex networking. Higher acceptance of pre-exposure prophylaxis (PrEP) was observed among testers. Overall, socioeconomic status played an important role in both HIV testing and access to PrEP. Interventions targeting sex networking venues and alternative means of testing provision are needed to increase coverage of HIV testing.