bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracisternal recombinant tissue plasminogen activator after aneurysmal subarachnoid hemorrhage
Authors: Findlay J. Max , Weir Bryce K. A. , Kassell Neal F. , Disney Lew B. , Grace Michael G. A. 
Published: May 2009

✓ Fifteen patients undergoing surgery within 48 hours of aneurysm rupture were administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after minimal surgical clot removal and aneurysm clipping. Preoperatively, 13 patients had diffuse or localized thick subarachnoid blood clots on computerized tomography (CT), and two had diffuse thin clots. The rt-PA was given as a single intraoperative injection of 7.5 mg (one patient), 10 mg (nine patients), or 15 mg (five patients). Postoperative cisternal drainage was employed in three patients.
All patients except one demonstrated partial to complete cisternal clot clearance on CT scans within 24 hours after surgery. The patient who showed no clot reduction was the only patient in this series to develop symptomatic vasospasm and was the only fatality, dying 8 days after rupture. No vasospasm was seen on follow-up cerebral angiography in six of the 14 responding patients, and mild-to-moderate arterial narrowing was seen in at least one major cerebral artery in the remaining eight patients. Severe angiographic vasospasm was not seen, although the patient who died did not undergo repeat angiography. There was one major complication early in the series which seemed clearly related to treatment, and that was a large extradural hematoma occurring within several hours of craniotomy. Intrathecal fibrinolytic treatment appears effective in clearing subarachnoid clot and reducing vasospasm, and may be associated with acceptable risks if given to patients with large-volume subarachnoid hemorrhages at high risk for severe vasospasm.
Evaluation and treatment of atlas burst fractures (Jefferson fractures)
Authors: Kesterson Lee , Benzel Edward , Orrison William , Coleman James 
Published: May 2009

✓ Although several large series of atlas fractures have been reported recently, none has concentrated on the evaluation and treatment of atlas burst fractures (Jefferson fractures). The treatment of this fracture is challenging. Its diagnosis may easily be missed due to concerns about associated trauma and absence of neurological signs. In addition, the open-mouth anteroposterior x-ray study, which is usually pathognomonic for the diagnosis, is often inadequate or not obtained. In order to clarify the diagnosis and treatment of this disorder, 17 cases of Jefferson fracture treated between 1982 and 1989 at the Louisiana State University Affiliated Hospitals are presented.
The diagnosis was delayed in three patients because of a low index of suspicion and inadequate x-ray films. Four patients were noted to have unstable Jefferson fractures; all of these had an associated Type II odontoid fracture and were treated with occiput-C-2 wiring and fusion. The remainder of the patients had stable Jefferson fractures and were managed with Minerva jackets or rigid collar stabilization. No significant complications related to the treatment of the Jefferson fracture occurred in this series. One patient died from associated injuries: however, the remaining patients enjoyed an excellent long-term result with the acquisition of spinal stability and the resolution of subjective complaints.
Efficacy of dorsal longitudinal myelotomy in treating spinal spasticity: a review of 20 cases
Authors: Putty Timothy K. , Shapiro Scott A. 
Published: May 2009

✓ The authors report their experience using dorsal longitudinal myelotomy in treating spasticity in 20 patients with complete spinal cord injuries. These patients suffered from severe painful flexor/extensor spasms that prevented them from wheelchair ambulation and/or their decubitus ulcers healing. All were receiving large doses of various oral drugs, including baclofen, which had failed to control their spasticity, and all underwent a modification of a posterior T-myelotomy as first described by Bischof. All 20 patients enjoyed immediate complete relief of their painful spasms, although two (10%) eventually experienced return of their spasms and are thus classified as long-term failures. Seventeen patients succeeded in markedly reducing, or being completely weaned from, their antispasmodic medications. In 11 of 14 patients, nonhealing decubitus ulcers subsequently healed with treatment. Bladder function was unchanged from the preoperative status in all patients.
Chronic intrathecal baclofen infusion has recently been reported as an effective treatment of the spasticity of paraplegia. The results of this study, along with previous reports advocating dorsal longitudinal myelotomy, suggest that this approach is an efficacious alternative to chronic baclofen infusion in reducing spasticity for complete paraplegics. Considering the cost of the infusion pump, along with the fact that chronic intrathecal baclofen therapy necessitates long-term medical supervision, it appears that myelotomy is superior for this select group of patients who have no hope of regaining voluntary motor function.
Surgical manipulation of primate cerebral arteries in established vasospasm
Authors: Findlay J. Max , Macdonald R. Loch , Weir Bryce K. A. , Grace Michael G. A. 
Published: May 2009

✓ It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported.
Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (> 40% reduction in vessel caliber compared to baseline, p < 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation.
Radiation-induced meningiomas: experience at the Mount Sinai Hospital and review of the literature
Authors: Harrison Michael J. , Wolfe David E. , Lau Tai-Shing , Mitnick Robin J. , Sachdev Ved P. 
Published: May 2009

✓ From the records of The Mount Sinai Hospital, seven cases which met established criteria for radiation-induced meningiomas were identified. This represents the largest series of radiogenic meningiomas documented in North America and includes both intracranial and intraspinal tumors. The records and pathological specimens were reviewed and these data analyzed with other cases retrieved from the world literature. This study reveals that radiation-induced meningiomas can be categorized into three groups based on the amount of radiation administered: 1) low dose; 2) moderate dose and miscellaneous; and 3) high dose. The overwhelming majority of cases had received low-dose irradiation (800 rad) to the scalp for tinea capitis and the second largest group resulted from high-dose irradiation for primary brain tumors (> 2000 rad).
The unique features distinguishing radiation-induced meningiomas from other meningiomas are reviewed. Although histologically atypical tumors were common in this series, overt malignancy was not encountered. The preoperative management of these lesions should include angiography to evaluate for large-vessel occlusive vasculopathy, a known association of meningiomas induced by high-dose irradiation. Given the propensity these tumors possess for recurrence, a wide bony and dural margin is recommended at surgical resection.
The natural history of intracranial venous angiomas
Authors: Garner Timothy B. , Curling O. Del , Kelly David L. , Laster D. Wayne 
Published: May 2009

✓ Cerebral venous angiomas are congenital anomalies of the intracranial venous drainage. Many believe that they are associated with a high risk of hemorrhage and neurological dysfunction, but newer neurodiagnostic imaging techniques are showing not only that they are more common than previously known but also that many have no associated symptoms. In this retrospective study, the natural history of venous angiomas was examined in 100 patients (48 males and 52 females) with radiographically identifiable lesions treated over a 14-year period. Information on the natural history of the lesion was obtained from clinical records and follow-up data. Imaging studies included angiography, computerized tomography, and magnetic resonance imaging. Angioma locations were classified as frontal (42 cases), parietal (24 cases), occipital (4 cases), temporal (2 cases), basal or ventricular (11 cases), cerebellar (14 cases), or brain stem (3 cases); 47 lesions were on the left side.
Headache as a presenting symptom was common (36 patients) and often led to other radiographic studies, but this appeared to be related to the vascular lesion in only four patients. Other possibly related complications were hemorrhage in one patient, seizures in five, and transient focal deficits in eight. Fifteen patients had no neurological signs or symptoms. The mean patient age at last contact was 45.3 years (range 3 to 94 years). All patients have been managed without surgery. It is concluded that significant complications secondary to venous angiomas are infrequent and that surgical resection of these lesions and of surrounding brain is rarely indicated.
Long-term outcome of 89 low-grade brain-stem gliomas after interstitial radiation therapy
Authors: Mundinger Fritz , Braus Dieter F. , Krauss Joachim K. , Birg Walter 
Published: May 2009

✓ Between 1974 and 1985, 89 patients suffering from histologically confirmed, nonresectable low-grade astrocytomas located in the brain stem were entered into a retrospective study. Iodine-125 (125I) was implanted in 29 patients and iridium-192 (192Ir) in 26 patients. Computerized tomography revealed that 78% of the tumors in these patients were located chiefly in the mesencephalic region, 70% were circumscribed, and 78% were contrast-enhanced. Thirty-four patients underwent biopsy without prior aggressive tumor-specific therapy such as chemotherapy or external beam irradiation. Among these, 70% of the tumors were located predominantly in the pons, 74% were diffuse, and 59% were hypodense or isodense after contrast enhancement. Long-term follow-up investigations indicated that life expectancy after interstitial radiation therapy with 125I implanted directly by catheter either permanently or temporarily showed a more favorable trend than that after treatment with 192Ir.
Interstitial radiation therapy with 125I appears to be an effective treatment for slowly proliferating, differentiated, well-delineated, nonresectable brain-stem gliomas. This technique makes it possible to achieve radio-surgical tumor control and, when carefully applied, represents the least traumatic treatment. Reduction of the tumor mass brings about improvement of the clinical symptoms. Further investigations on the biological behavior of brain-stem gliomas and prospective randomized long-term follow-up studies are necessary to evaluate the different kinds of treatment available for these patients.
Operative management of bilateral facet dislocation
Authors: Wolf Aizik , Levi Lion , Mirvis Stuart , Ragheb John , Huhn Stephen , Rigamonti Daniele , Robinson Walker L. 
Published: May 2009

✓ Fifty-two patients with acute traumatic bilateral locked facets were treated at one trauma center during a 3½-year period (July, 1987, to December, 1990). The patients presented with complete motor quadriplegia (34 cases), incomplete myelopathy (13 cases), or intact long-tract function (five cases). The injuries occurred at C2–3 (one patient, with intact function), C4–5 (12 patients), C5–6 (16 patients), C6–7 (19 patients), and C7—T1 (four patients).
Immediate traction (with increasing weight and serial x-ray studies) and/or induction of general anesthesia and muscle relaxation reduced the dislocation in 40 patients, but 12 needed prompt operative reduction as their injuries failed to reduce within 4 hours. Stabilization was indicated for all patients, but three did not undergo surgery: two elderly patients with complete injuries (one refused surgery and one died), and one patient with multiple injuries (fusion was achieved by halo-vest immobilization for 3 months). Of the 49 patients treated operatively, 23 (44.2%) underwent surgery on the day of injury and 26 on a delayed basis (mean 8.7 days postinjury). Surgical treatment included fusion of the posterior facet to a spinous process (44 cases), an anterior Caspar plate technique (three cases), and both procedures (two cases). Of these 49 patients, three (6.1%) with complete injuries died due to an adult respiratory distress syndrome.
Improvement of cord function, judged by functional grade change, was observed at discharge in 15 patients (31.9%) and in 15 (71.4%) of the 21 patients with a 1-year follow-up period. Of the 34 patients with complete myelopathy on admission, three are ambulatory after 1 year, and 13 others have gained function in at least one nerve root. It is concluded that prompt reduction (nonoperative or surgical) and internal stabilization facilitate recovery even in neurologically compromised patients, and that early operative intervention is a wiser option than conservative management. This report also documents a higher incidence of this injury without deficit (five of the 52 cases) than reported in other series.
Disabling cerebral transient ischemic attacks
Authors: McCormick Patrick W. , Tomecek Frank J. , McKinney Jean , Ausman James I. 
Published: May 2009

✓ The surgical management of an emerging clinical entity, namely disabling transient cerebral ischemic attacks, is described. A series of 19 patients treated in a 2-year period (12 with anterior circulation dysfunction and seven with posterior insufficiency) met the following criteria: 1) stereotypical recurrent episodes of transient neurological dysfunction related to the anterior or posterior circulation distribution; 2) failure of maximum medical therapy to control the transient neurological dysfunction; 3) four-vessel cerebral angiography demonstrating an isolated vascular territory corresponding to patient symptoms; 4) inhalation xenon cerebral blood flow studies with at least three of eight probe-pairs showing significant asymmetries in the initial slope index, localizing an area of relative oligemia to the symptomatic hemisphere (anterior circulation only); and 5) severe restriction of lifestyle due to transient ischemic attacks (TIA's). Seventeen patients underwent surgical bypass therapy: deep sylvian superficial temporal artery (STA)-middle cerebral artery (MCA) bypass in nine; surface STA-MCA bypass in three: STA-superior cerebellar artery bypass in three; STA-posterior cerebral artery bypass in one; and aorta-carotid artery bypass in one. There was one perioperative death and four perioperative strokes (two ipsilateral and two contralateral to the operated side). The average follow-up period was 14 months. Of the 16 surviving surgically treated patients, 13 (81%) have had an excellent to good outcome with complete resolution of TIA's and minimal neurological deficits. Three patients had a poor outcome with either a significant persistent neurological deficit or continued TIA's. The two patients not treated surgically continue to have vertebrobasilar insufficiency episodes while receiving oral anticoagulation medication. The overall mortality rate (5.5%) and stroke morbidity rate (22.2%) of surgical therapy for disabling TIA's are high in this neurologically unstable group of patients, but are associated with an 81 % excellent to good response.
Although the natural history of disabling TIA's is not known, these patients present with significant to total disability due to their symptoms. It is concluded that disabling TIA's respond to surgical revascularization and may represent an indication for cerebral revascularization surgery.
Lipopolysaccharide-Induced Apoptosis in Transformed Bovine Brain Endothelial Cells and Human Dermal Microvessel Endothelial Cells: The Role of JNK
Authors: Karahashi Hisae , Michelsen Kathrin S. , Arditi Moshe 
Published: May 2009

Abstract
Stimulation of transformed bovine brain endothelial cells (TBBEC) with LPS leads to apoptosis while human microvessel endothelial cells (HMEC) need the presence of cycloheximide (CHX) with LPS to induce apoptosis. To investigate the molecular mechanism of LPS-induced apoptosis in HMEC or TBBEC, we analyzed the involvement of MAPK and PI3K in TBBEC and HMEC. LPS-induced apoptosis in TBBEC was hallmarked by the activation of caspase 3, caspase 6, and caspase 8 after the stimulation of LPS, followed by poly(ADP-ribose) polymerase cleavage and lactate dehydrogenase release. We also observed DNA cleavage determined by TUNEL staining in TBBEC treated with LPS. Herbimycin A, a tyrosine kinase inhibitor, and SP600125, a JNK inhibitor, suppressed the activation of caspases and lactate dehydrogenase release. Moreover, a PI3K inhibitor (LY294002) suppressed activation of caspases and combined treatment with both SP600125 and LY294002 completely inhibited the activation of caspases. These results suggest that the JNK signaling pathway through the tyrosine kinase and PI3K pathways is involved in the induction of apoptosis in LPS-treated TBBEC. On the other hand, we observed sustained JNK activation in HMEC treated with LPS and CHX, and neither ERK1/2 nor AKT were activated. The addition of SP600125 suppressed phosphorylation of JNK and the activation of caspase 3 in HMEC treated with LPS and CHX. These results suggest that JNK plays an important role in the induction of apoptosis in endothelial cells.
Suppression of NF-κB by Cyclosporin A and Tacrolimus (FK506) via Induction of the C/EBP Family: Implication for Unfolded Protein Response
Authors: Du Shuqi , Hiramatsu Nobuhiko , Hayakawa Kunihiro , Kasai Ayumi , Okamura Maro , Huang Tao , Yao Jian , Takeda Masayuki , Araki Isao , Sawada Norifumi , Paton Adrienne W. , Paton James C. , Kitamura Masanori 
Published: May 2009

Abstract
Immunosuppressive agents cyclosporin A (CsA) and tacrolimus (FK506) inhibit cytokine production by activated lymphocytes through interfering with calcineurin. However, little is known about their effects on the function of nonlymphoid cells. We found that, in renal tubular cells, induction of MCP-1 by inflammatory cytokines was blunted by CsA and FK506. This suppression was correlated with induction of unfolded protein response (UPR) evidenced by endogenous and exogenous indicators. The induction of UPR by these agents was reversible and observed generally in other nonimmune cells. Furthermore, administration with CsA in reporter mice caused rapid, systemic induction of UPR in vivo. In TNF-α-treated cells, suppression of MCP-1 by CsA or FK506 was associated with blunted responses of NF-κB, the crucial regulator of MCP-1. The suppression of NF-κB was reproduced by other inducers of UPR including AB5 subtilase cytotoxin, tunicamycin, thapsigargin, and A23187. CsA and FK506, as well as other UPR inducers, caused up-regulation of C/EBP family members, especially C/EBPβ and CHOP (C/EBP homologous protein), and overexpression of either C/EBPβ or CHOP significantly attenuated TNF-α-triggered NF-κB activation. Furthermore, down-regulation of C/EBPβ by small interfering RNA substantially reversed the suppressive effect of CsA on TNF-α-induced MCP-1 expression. These results suggested that CsA and FK506 confer insensitiveness to TNF-α on resident cells through UPR-dependent induction of the C/EBP family members.
Granulysin Induces Cathepsin B Release from Lysosomes of Target Tumor Cells to Attack Mitochondria through Processing of Bid Leading to Necroptosis
Authors: Zhang Honglian , Zhong Chao , Shi Lei , Guo Yuming , Fan Zusen 
Published: May 2009

Abstract
Granulysin is a killer effector molecule localized in cytolytic granules of human NK and CTL cells. Granulysin exhibits broad antimicrobial activity and potent cytotoxic action against tumor cells. However, the molecular mechanism of granulysin-induced tumor lysis is poorly understood. In this study, we found that granulysin causes a novel cell death termed necroptosis. Granulysin can target lysosomes of target tumor cells and induce partial release of lysosomal contents into the cytosol. Relocalized lysosomal cathepsin B can process Bid to active tBid to cause cytochrome c and apoptosis-activating factor release from mitochondria. Cathepsin B silencing and Bid or Bax/Bak deficiency resists granulysin-induced cytochrome c and apoptosis-activating factor release and is less susceptible to cytolysis against target tumor cells.
Myeloid-Specific Deletion of Tumor Suppressor PTEN Augments Neutrophil Transendothelial Migration during Inflammation
Authors: Sarraj Bara , Massberg Steffen , Li Yitang , Kasorn Anongnard , Subramanian Kulandayan , Loison Fabien , Silberstein Leslie E. , von Andrian Ulrich , Luo Hongbo R. 
Published: May 2009

Abstract
Phosphatidylinositol 3,4,5-trisphosphate (PIP3) is a second messenger that is involved in a number of cell activities including cell growth, proliferation, and motility. PIP3 is produced by PI3K and regulated by PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SHIP lipid phosphatases. Evidence from our experiments shows that enhanced PIP3 production results in elevated neutrophil recruitment under inflammatory conditions. However, the mechanism of this elevation is not well understood. We used intravital video microscopy to investigate neutrophil recruitment in the cremaster venules of wild-type and PTEN knockout (KO) mice. Neutrophil transmigration was augmented in PTEN KO mice 4 h after TNF-α intrascrotal injection. PTEN KO neutrophils also showed significantly enhanced transmigration 2 h after MIP-2 intrascrotal injection, an effect that dramatically decreased when PI3K or Src kinase inhibitor treatments preceded MIP-2 stimulation. Similarly, fMLP superfusion of the cremaster muscle lead to enhanced emigration in PTEN KO mice. The observed elevation in neutrophil emigration was likely caused by increased speed of crawling, crossing the venular wall, and migrating through the muscular tissue in PTEN KO mice because the effect of PTEN depletion on neutrophil rolling or adhesion was minimal. Interestingly, chemoattractant-induced release of gelatinase and elastase was also elevated in PTEN null neutrophils, providing a potential mechanism for the enhanced neutrophil migration in the PTEN KO mice. Collectively, these results demonstrate that PTEN deletion in neutrophils enhances their invasivity and recruitment to inflamed sites more likely by raising the cell physical capability to cross the vascular and tissue barriers.