Outcomes of endovascular coiling of anterior communicating artery aneurysms in the early post-rupture period: a prospective analysis.

BACKGROUND: There have been significant advances in the technical aspects of endovascular therapy of cerebral aneurysms. Anterior communicating artery (Acom A) aneurysms were traditionally treated by surgical clipping. Endovascular coiling has the distinct advantage of being minimally invasive and can be performed anytime during the course of subarachnoid hemorrhage (SAH). AIMS: To evaluate the results of endovascular coiling of Acom A aneurysms in the early post-rupture period. MATERIAL AND METHODS: Between June 1999 and December 2009, 103 Acom A aneurysms were treated with endovascular coiling. All the patients underwent digital subtraction angiography (DSA) and a diagnostic 3D rotational angiogram (3D-RA), followed by coiling using dedicated intracranial coils. RESULTS: Of the 103 patients coiled, 52% presented in Fischer grade 3/4 SAH and 13.5% in Hunt and Hess grade 4/5. Technical success was 98%. Complete obliteration of the aneurysm was achieved in 97 (94%) patients. Only one patient died of direct procedure-related complication due to coil prolapse. None of the patients had rebleeds. Six-month check angiogram performed in 34 patients showed significant recanalization in one patient. CONCLUSION: Ruptured Acom A aneurysms are implicated in majority of cases of SAH. Our results support the latest guideline "that endovascular coil occlusion of the aneurysm is appropriate for patients with a ruptured cerebral artery aneurysm that is deemed treatable either by endovascular coiling or by surgical clipping."

Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4.

CXCR4, a seven transmembrane domain G-protein-coupled receptor for the Cys-X-Cys class of chemokines, is one of several chemokine receptors that can act as a co-receptor with CD4 for the human immunodeficiency virus (HIV-1) glycoprotein gp120 [1-3]. CXCR4 can mediate the entry of HIV-1 strains that specifically infect T cells, such as the IIB strain (see [4] for review). Recent reports indicate that gp120 can signal through CXCR4 [5] and it has been suggested that signal transduction, mediated by the viral envelope, might influence viral-associated cytopathicity or apoptosis [6]. Neuronal apoptosis is a feature of HIV-1 infection in the brain [7,8], although the exact mechanism is unknown. Here, we address the possible role of CXCR4 in inducing apoptosis using cells of the hNT human neuronal cell line; these cells resemble immature post-mitotic cholinergic neurons and have a number of neuronal characteristics [9-15]. We have previously shown that gp120 from the HIV-1 IIIB strain binds with high affinity to CXCR4 expressed on hNT neurons [15]. We now find that both IIIB gp120 and the Cys-X-Cys chemokine SDF-1 alpha can directly induce apoptosis in hNT neurons in the absence of CD4 and in a dose-dependent manner. To our knowledge, this is the first report of a chemokine and an HIV-1 envelope glycoprotein eliciting apoptotic responses through a chemokine receptor.

HIV infection and aging: mechanisms to explain the accelerated rate of progression in the older patient.

Age is an important predictor of progression in HIV infections. Not only do older individuals' develop AIDS more rapidly than younger persons, they die more quickly after developing an AIDS-defining illness. While the elderly have higher morbidity and mortality rates from viral and bacterial infections, the mechanism(s) responsible for the more rapid progression of HIV infection in older individuals has not been described. Our results demonstrate that the destruction of T cells in both young and old HIV infected patients progresses at the same rate. HIV 1-infected cells from older individuals do not appear more susceptible to immune mediated destruction. The more rapid progression appears due to an inability of older persons to replace functional T cells that are being destroyed. These findings suggest that improved survival in older HIV infected individuals will require more aggressive antiretroviral therapies as well as continued research to identify and preserve immune system elements that control the virus.

Simian immunodeficiency virus SIVsmmPBj 1.9 induces multinucleated giant cell formation in human peripheral blood monocytes.

SIVsmmPBJ 1.9 is an extremely virulent clone of the simian immunodeficiency virus SIVsmmPBj 14 that causes an acute lethal disease in pigtail macaques, with death occurring 6 to 8 days after infection. The disease is characterized by bloody mucoid diarrhea, lymphoid hyperplasia, and giant cell pneumonia. We have developed an in vitro model for the production of multinucleated giant cells (MGCs) in which peripheral blood monocytes rapidly fuse to form MGCs when cultured in lymphocyte-conditioned medium and antibody against class II MHC. We have tested the effect of SIVsmmPBj on monocytes in our MGC model system. Peripheral blood mononuclear cells (PBMCs) from normal healthy human subjects, when cultured in the presence of anti-class II MHC monoclonal antibody and SIVsmmPBj 1.9, but not either alone, resulted in the formation of MGCs within 4 days. Experiments using Transwell chambers indicated that such MGCs are formed by fusion of monocytes, not by virus-induced fusion of lymphocytes. SIVsmmPBj 1.9 is unique in inducing MGC formation in that other SIV and HIV isolates do not induce MGCs. Whereas SIVsmmPBj 1.9 grown in PBMCs was a potent inducer of MGCs in the presence of anti-class II MHC antibody, SIVsmmPBj 1.9 grown in CEMx174 failed to do so. Antibodies against IFN-gamma and TNF-alpha significantly inhibited SIVsmmPBj/anti-class II-induced formation of MGCs. These results indicate that cytokines released in response to SIVsmmPBj 1.9, in conjunction with antibodies to class II MHC, caused fusion of monocytes.

Presence in India of HIV type 1 similar to North American strains.

PIP: HIV-1 vaccine candidates being tested in the US and Europe are mainly based upon subtype B strains. Worldwide, however, there are multiple strains of HIV against which vaccines must also be developed. The authors present methodology and findings from an investigation into which subtypes of HIV-1 are present in an urban center in southern India. Lymphocyte and serum samples were collected from HIV-1 infected patients attending an outpatient screening clinic at Apollo Hospital, a private urban hospital in Hyderabad, Andhra Pradesh. Sera were tested and confirmed with ELISA and Western blot for the presence of antibody to HIV-1, with peripheral blood leukocytes obtained from five of the patients through density gradient centrifugation of fresh blood and subsequently shipped at -70 degrees Celsius to Johns Hopkins University where they were subjected to polymerase chain reaction and neutralization assays. No information was available about when the individuals became infected with HIV-1 and only limited clinical and risk factor data were available. In contrast to previous reports of exclusively subtype C strains in India, the study found and presents the first published evidence of the presence of subtype B HIV-1 in the country. The sequences identified in the study appear to be more similar to subtype B isolates from North America and Europe than those reported from Thailand, and are distinct from a subtype B sequence collected in 1992 from Vellore in southeast India. The presence of neutralizing activity against subtype B strains from sera matched with the phylogenetic analysis provides strong evidence for the presence of HIV-1 subtype B infection in India. It would not be surprising if additional HIV-1 subtypes were detected in India given the frequent travel which occurs between India and Europe, North America, Africa, and other areas of Asia including Thailand. These results underscore the necessity for a comprehensive and nationwide analysis of HIV-1 strain variation throughout India in the interest of developing and disseminating an effective vaccine against HIV-1 in India.^ieng

Implications of a permanent cardiac pacemaker in peripheral nerve blockade.

Patients with permanent cardiac pacemakers (PPMs) are vulnerable to electromagnetic interference from electrical equipment used in the operating room environment. Electromagnetic interference may lead to PPM malfunction with potential harmful effects to the patient. Conventional techniques for peripheral nerve blockade include the use of electrical nerve stimulation (NS) for nerve localization. The hazards of NS, especially when applied near the implanted PPM sites, are not known. In the absence of available guidelines regarding the safe use of NS in the setting of an implanted PPM, we recommend a combined guidance approach for peripheral nerve blockade using ultrasound for nerve localization along with low-current NS for nerve identification.

The role of a preprocedure systematic sonographic survey in ultrasound-guided regional anesthesia.

BACKGROUND AND OBJECTIVES: The presence of neurovascular abnormalities may increase the risk of complications following regional anesthesia techniques. Use of conventional nerve localization methods may fail to detect such abnormalities and potentially result in block failure and/or unintentional neurovascular injury. METHODS: We use 2 examples to illustrate this, and the concept that systematic use of a preprocedure ultrasound (US) scan may serve as an aid both for diagnosis of abnormal anatomy, and in planning the appropriate anesthetic technique. RESULTS: Use of a preprocedure US scan helped to diagnose abnormal anatomy and assisted in planning a more appropriate anesthetic technique. CONCLUSIONS: We believe that a systematic sonographic survey prior to regional anesthesia can be a valuable bedside screening tool to assess the suitability and challenges involved in performing US-guided peripheral nerve block.

Oxidative requirement for degranulation of human peripheral blood eosinophils.

Eosinophils possess both oxygen-dependent and oxygen-independent mechanisms for damaging helminthic parasites such as schistosomula. We have studied the release of the granular enzymes beta-glucuronidase and arylsulfatase to evaluate the oxidative requirement for degranulation. Both ionophore-mediated and immunoglobulin G-mediated release of granular enzymes were enhanced in the presence of oxygen (P less than or equal to 0.05). Calcium ionophore-mediated degranulation under aerobic conditions was reduced by the addition of the degradative enzymes catalase and superoxide dismutase, suggesting that active oxygen products enhance degranulation. In contrast, oxygen products did not appear to contribute to degranulation induced by immunoglobulin G-coated beads.

Selective regulation of eosinophil degranulation by interleukin 1 beta.

Recent evidence confirms that cytokines such as IL-1, IL-4, IL-5, and GM-CSF may enhance or inhibit eosinophil function. Functions that are susceptible to modulation include eosinophil-mediated antibody-dependent damage of helminthic parasites, oxidative metabolism and degranulation. We have employed IgG and IgE-coated Sepharose beads to investigate selective modulation of IgG and IgE-mediated enzyme release by IL-1 beta. Both IgG and IgE-coated beads induced release of granular enzymes beta-glucuronidase and arylsulfatase. Enzyme release from IgG-stimulated eosinophils was inhibited by preincubation with IL-1 beta (100 pg/ml, P less than or equal to 0.05). In contrast, enzyme release by IgE-stimulated eosinophils was enhanced by IL-1 beta (100 pg/ml, P less than or equal to 0.05). These studies support the hypothesis that IL-1 beta has specific selective actions on eosinophil function. Furthermore, these actions on particle-stimulated enzyme release suggest that IgG and IgE mediated processes in eosinophils are differentially regulated.

Inhibition of IgG-triggered human eosinophil function by IL-4.

Triggering of eosinophil secretory and cytotoxic functions by stimulation of the IgG and IgE FcR is thought to have major importance in the pathophysiology of tissue eosinophilia. We studied the ability of human rIL-4 to regulate this triggering event in human eosinophils. At doses ranging from 0.1 to 10 pg/ml, IL-4 suppressed eosinophil secretion of beta-glucuronidase and arylsulfatase by up to 65% after stimulation with IgG-coated Sepharose beads. This effect required prolonged preincubation (16 h) of eosinophils with IL-4; no effect was detected after 1 h preincubation. Enzyme secretion stimulated by IgE-coated beads was not affected. Further, IL-4 (after 16 h preincubation), suppressed eosinophil antibody-dependent killing of schistosomula (Schistosoma mansoni) targets by 24 to 39% in four experiments (p less than 0.05). Flow microfluorimetry analysis showed that IL-4 reduced the expression of IgG FcR, but not IgE FcR, suggesting that this mechanism underlies the suppression of IgG-mediated secretion. Taken collectively, these results demonstrate a mechanism for T lymphocyte suppression of IgG-stimulated eosinophil functions via IL-4.

Anti-HLA class I antibody inhibits Staphylococcus enterotoxin A (SEA)-induced proliferation of human PBMC.

The antigen-presenting role of major histocompatibility complex (MHC) Class I molecules in the activation of appropriately restricted T cells is well documented. Now growing evidence indicates that MHC Class I molecules can, in addition, exert a regulatory effect and influence the resulting immune responses. In this report we show that a monoclonal antibody (mAb) directed against a conserved region of the human leukocyte antigens (HLA)-A, -B, and -C was able to inhibit proliferation of human peripheral blood mononuclear cells induced by the superantigen, Staphylococcus enterotoxin A. While anti-HLA inhibition was associated with a decrease in IL-2 receptor (IL-2R) expression, the addition of exogenous IL-2 did not restore the proliferative response in the presence of anti-HLA mAb. The inhibition of DNA synthesis was also associated with a decrease in the expression of the early activation marker CD69. These results suggest a critical role for HLA Class I molecules in the early events of human lymphocyte activation and proliferation as well as in their expression of the IL-2R.

Antiapoptotic signaling by the insulin receptor in Chinese hamster ovary cells.

We have sought to determine whether insulin can promote cell survival and protect Chinese hamster ovary (CHO) cells from apoptosis induced by serum starvation. Low concentrations of insulin were antiapoptotic for cells overexpressing wild-type insulin receptors but not in cells transfected with kinase-defective insulin receptor mutants that lacked a functional ATP binding site. However, treatment with orthovanadate (50 microM), a widely used tyrosine phosphatase inhibitor, led a dramatic reduction in internucleosomal DNA fragmentation in both cell lines. Cells transfected with truncated receptor mutants in either the juxtamembrane or C-terminal domain were as responsive as cells overexpressing wild-type receptors in mediating insulin antiapoptotic protection. The mechanisms underlying insulin antiapoptotic protection were investigated using a variety of pharmacological tools known to inhibit distinct signaling pathways. The phosphatidylinositol-3' kinase inhibitors wortmannin and LY294002 had only a modest influence whereas blocking protein farnesylation with manumycin severely disrupted the antiapoptotic capacity of the insulin receptor. Of interest, cells gained antiapoptotic potential following inhibition of extracellular signal-regulated kinase activation with the pharmacological agent PD98059. Insulin induced MKK3/MKK6 phosphorylation and activation of p38 MAP kinase whose activity was inhibited with SB203580. However, the inhibition of p38 MAP kinase had no effect on the protection offered by insulin. We conclude that the antiapoptotic function of the insulin receptor requires intact receptor kinase activity and implicates a farnesylation-dependent pathway. Increase in cellular phosphotyrosine content, however, triggers antiapoptotic signal that may converge downstream of the insulin receptor.