bluuebunny/crossref_metadata_2025 huggingface dataset:
Endo‐Porter: A Novel Reagent for Safe, Effective Delivery of Substances into Cells
Authors: SUMMERTON JAMES E.
Published: January 2006

Delivering large molecules into the cytosol of animal cells without damaging the cells has been one of the toughest challenges in biology. Endo‐Porter is a weak‐base amphiphilic peptide that was designed to deliver morpholino antisense oligomers and other non‐ionic substances into the cytosol/nuclear compartment of cells by an endocytosis‐mediated process that avoids damaging the plasma membrane of the cell. This prevents the loss of vital cell contents and the attendant high cell toxicity typical of most delivery systems. To deliver a substance into cells simply add that substance to the medium covering the cells, followed by addition of the pre‐formulated Endo‐Porter solution and swirl to mix. While most delivery reagents begin to show serious toxicity after just a few hours and are relatively ineffective in the presence of serum, delivery with Endo‐Porter may be continued for 24 hours, or even 48 hours, without undue toxicity, and Endo‐Porter is particularly effective in the presence of the 10% serum commonly used with cultured cells. The mechanism of delivery, entails rapid adsorption of Endo‐Porter to cell surfaces, but this adsorption to the cell surface does not damage the plasma membrane. The membrane‐bound Endo‐Porter is rapidly endocytosed, along with any substances present in the medium (ie., the cargo one wishes to deliver). Upon subsequent acidification of the endosome (a natural process) the Endo‐Porter contained within that endosome is converted to its poly‐cationic form, which acts to permeabilize the endosomal membrane. This acid‐induced permeabilization of the endosomal membrane allows any co‐endocytosed cargo to pass from the endosome into the cytosol of the cell. This paper describes the basic design strategy used to develop Endo‐Porter, test systems used to guide that development, and the effects of various structural parameters, including size and composition of the lipophilic face, size and composition of the weak‐base face, and the relationship between peptide length and delivery efficiency in the presence of serum.
The Development of Bioactive Triple Helix‐Forming Oligonucleotides
Authors: SEIDMAN MICHAEL M. , PURI NITIN , MAJUMDAR ALOKES , CUENOUD BERNARD , MILLER PAUL S. , ALAM ROWSHON
Published: January 2006

We are developing triple helix‐forming oligonucleotides (TFOs) as gene targeting reagents in mammalian cells. We have described psoralen‐conjugated TFOs containing 2′‐O‐methyl (2′OMe) and 2′‐O‐aminoethoxy (AE) ribose substitutions. TFOs with a cluster of 3‐4 AE residues, with all other sugars as 2′OMe, were bioactive in a gene knockout assay in mammalian cells. In contrast, TFOs with one or two clustered, or three dispersed, AE residues were inactive. Thermal stability analysis of the triplexes indicated that there were only incremental differences between the active and inactive TFOs. However the active and inactive TFOs could be distinguished by their association kinetics. The bioactive TFOs showed markedly greater on‐rates than the inactive TFOs. It appears that the on‐rate is a better predictor of TFO bioactivity than thermal stability. Our data are consistent with a model in which a cluster of 3‐4 AE residues stabilizes the nucleation event that precedes formation of a complete triplex. It is likely that triplexes in cells are much less stable than triplexes in vitro probably as a result of elution by chromatin‐associated translocases and helicases. Consequently the biologic assay will favor TFOs that can bind and rebind genomic targets quickly.
The Neuroprotective and Vasculo-Neuro-Regenerative Roles of Adrenomedullin in Ischemic Brain and Its Therapeutic Potential
Authors: Miyashita Kazutoshi , Itoh Hiroshi , Arai Hiroshi , Suganami Takayasu , Sawada Naoki , Fukunaga Yasutomo , Sone Masakatsu , Yamahara Kenichi , Yurugi-Kobayashi Takami , Park Kwijun , Oyamada Naofumi , Sawada Naoya , Taura Daisuke , Tsujimoto Hirokazu , Chao Ting-Hsing , Tamura Naohisa , Mukoyama Masashi , Nakao Kazuwa
Published: December 2005

Adrenomedullin (AM) is a vasodilating hormone secreted mainly from vascular wall, and its expression is markedly enhanced after stroke. We have revealed that AM promotes not only vasodilation but also vascular regeneration. In this study, we focused on the roles of AM in the ischemic brain and examined its therapeutic potential. We developed novel AM-transgenic (AM-Tg) mice that overproduce AM in the liver and performed middle cerebral artery occlusion for 20 min (20m-MCAO) to examine the effects of AM on degenerative or regenerative processes in ischemic brain. The infarct area and gliosis after 20m-MCAO was reduced in AM-Tg mice in association with suppression of leukocyte infiltration, oxidative stress, and apoptosis in the ischemic core. In addition, vascular regeneration and subsequent neurogenesis were enhanced in AM-Tg mice, preceded by increase in mobilization of CD34+ mononuclear cells, which can differentiate into endothelial cells. The vasculo-neuro-regenerative actions observed in AM-Tg mice in combination with neuroprotection resulted in improved recovery of motor function. Brain edema was also significantly reduced in AM-Tg mice via suppression of vascular permeability. In vitro, AM exerted direct antiapoptotic and neurogenic actions on neuronal cells. Exogenous administration of AM in mice after 20m-MCAO also reduced the infarct area, and promoted vascular regeneration and functional recovery. In summary, this study suggests the neuroprotective and vasculo-neuro-regenerative roles of AM and provides basis for a new strategy to rescue ischemic brain through its multiple hormonal actions.
Role of Prophet of Pit1 (PROP1) in Gonadotrope Differentiation and Puberty
Authors: Vesper Amanda H. , Raetzman Lori T. , Camper Sally A.
Published: December 2005

The prophet of Pit1 (PROP1) gene is essential for normal gonadotropin production in both humans and mice. Transgenic mice that overexpress PROP1 in gonadotropes and thyrotropes have transient hypogonadotropic hypogonadism and increased risk of pituitary adenomas. Here we report a temporal study of pituitary gonadotrope terminal differentiation and hypogonadism, delayed onset of puberty, and transient growth insufficiency in the transgenic males. The Prop1 transgenic mice recover from their abnormalities and exhibit normal size and fertility at 3 months. The relatively normal expression pattern of GnRH receptor (Gnrhr) suggests that the pituitary gonadotrope cell lineage is appropriately specified, but the ability to synthesize LH and FSH is impaired by excess PROP1. We report no obvious abnormalities in expression of the transcription factors early growth response 1, NR5A1, GATA2, TBX19, and NR0B1, or the TGFβ pathway members including activin, inhibin, and activin receptors. Thus, overexpression of PROP1 may influence gonadotrope development by a novel mechanism. Microarray analysis identified the inhibitory transmembrane receptor gene Klrg1 and the protease gene Prss28 as candidates for involvement in this process. We hypothesize that variation in PROP1 expression could affect the growth spurt and the onset of puberty in humans.
Expression of Growth Differentiation Factor 9 in the Oocytes Is Essential for the Development of Primordial Follicles in the Hamster Ovary
Authors: Wang Cheng , Roy Shyamal K.
Published: December 2005

Postnatal growth differentiation factor 9 (GDF-9) expression in the hamster oocytes precedes the formation of primordial follicles. We examined the functional significance of GDF-9 in primordial folliculogenesis in the hamster ovary using RNA interference knockdown of GDF-9 mRNA and protein expression. Fifteen-day-old fetal ovaries were cultured for 9 d with or without 1 ng FSH, 1 μl Metafectane, 100 nm control nontargeting small interfering RNA (siRNA), GDF-9 siRNA, or GDF-9 siRNA + FSH, and the development of primordial follicles examined. The efficiency of siRNA transfecting ovarian cells in the organ culture was tested by culturing ovaries with siGlo, a nontargeting control siRNA labeled with Cy3. More than 90% of cells in the ovary were siGlo positive, and neither the Metafectane nor the siRNA-induced cellular apoptosis. Control siRNA did not affect the basal levels of GDF-9 mRNA, but GDF-9 siRNA slightly but significantly reduced the level. FSH markedly up-regulated the levels of GDF-9 mRNA and protein, and the effect was completely suppressed by GDF-9 siRNA. However, GDF-9 siRNA did not affect the levels of bone morphogenetic protein receptor IA or β-actin mRNA. GDF-9 siRNA alone also reduced GDF-9 protein expression. Concurrent with GDF-9 expression, FSH significantly augmented primordial follicle formation, but the effect was abolished by GDF-9 siRNA. These results suggest that endogenous GDF-9 plays an important role in somatic cell differentiation and the formation of primordial follicles. Furthermore, FSH, by virtue of regulating GDF-9 expression, modulates oocyte regulation of primordial follicles formation.
Agouti-Related Protein Is Posttranslationally Cleaved by Proprotein Convertase 1 to Generate Agouti-Related Protein (AGRP)83–132: Interaction between AGRP83–132 and Melanocortin Receptors Cannot Be Influenced by Syndecan-3
Authors: Creemers John W. M. , Pritchard Lynn E. , Gyte Amy , Le Rouzic Philippe , Meulemans Sandra , Wardlaw Sharon L. , Zhu Xiaorong , Steiner Donald F. , Davies Nicola , Armstrong Duncan , Lawrence Catherine B. , Luckman Simon M. , Schmitz Catherine A. , Davies Rick A. , Brennand John C. , White Anne
Published: December 2005

Agouti-related protein (AGRP) plays a key role in energy homeostasis. The carboxyl-terminal domain of AGRP acts as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, thereby modulating the effects of carboxyl-terminal AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. In this study we found that AGRP is processed intracellularly after Arg79-Glu80-Pro81-Arg82. The processing site suggests cleavage by proprotein convertases (PCs). RNA interference and overexpression experiments showed that PC1/3 is primarily responsible for cleavage in vitro, although both PC2 and PC5/6A can also process AGRP. Dual in situ hybridization demonstrated that PC1/3 is expressed in AGRP neurons in the rat hypothalamus. Moreover, hypothalamic extracts from PC1-null mice contained 3.3-fold more unprocessed full-length AGRP, compared with wild-type mice, based on combined HPLC and RIA analysis, demonstrating that PC1/3 plays a role in AGRP cleavage in vivo. We also found that AGRP83–132 is more potent an antagonist than full-length AGRP, based on cAMP reporter assays, suggesting that posttranslational cleavage is required to potentiate the effect of AGRP at the MC4-R. Because AGRP is cleaved into distinct amino-terminal and carboxyl-terminal peptides, we tested whether amino-terminal peptides modulate food intake. However, intracerebroventricular injection of rat AGRP25–47 and AGRP50–80 had no effect on body weight, food intake, or core body temperature. Because AGRP is cleaved before secretion, syndecan-3 must influence food intake independently of the MC4-R.
Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated
Authors: Mousa Shaker A. , O’Connor Laura , Davis Faith B. , Davis Paul J.
Published: December 2005

We have recently described the proangiogenesis effects of thyroid hormone in the chick chorioallantoic membrane (CAM) model. Generation of new blood vessels from existing vessels was promoted 2- to 3-fold by either T4 or T3 at 10−8–10−7m total hormone concentrations. In the present studies, nanomolar concentrations of 3,5-diiodothyropropionic acid (DITPA), a thyroid hormone analog with inotropic but not chronotropic properties, exhibited potent proangiogenic activity that was comparable to that obtained with T3 and T4 in both the CAM model and in an in vitro three-dimensional human microvascular endothelial sprouting assay. The proangiogenesis effect of DITPA was inhibited by tetraiodothyroacetic acid, a thyroid hormone analog that competes with T4 and T3 for a novel cell surface hormone receptor site on integrin αvβ3. The thyroid hormone analogs DITPA, T4, and T4-agarose, as well as basic fibroblast growth factor (b-FGF) and vascular endothelial cell growth factor, demonstrated comparable proangiogenic effects in the CAM model and in the three-dimensional human microvascular endothelial sprouting model. The proangiogenesis effect of either DITPA or b-FGF was blocked by PD 98059, an inhibitor of the ERK1/2 signal transduction cascade. Additionally, a specific integrin αvβ3 small molecule antagonist, XT199, effectively inhibited the proangiogenesis effect of DITPA and b-FGF. Thus, the proangiogenesis actions of thyroid hormone and its analog DITPA are initiated at the plasma membrane, apparently at integrin αvβ3, and are MAPK dependent.
Prospective Staged Volume Radiosurgery for Large Arteriovenous Malformations: Indications and Outcomes in Otherwise Untreatable Patients
Authors: Sirin Sait , Kondziolka Douglas , Niranjan Ajay , Flickinger John C. , Maitz Ann H. , Lunsford L. Dade
Published: December 2005

OBJECTIVE:

The obliteration response of an arteriovenous malformation (AVM) to radiosurgery is strongly dependent on dose and volume. For larger volumes, the dose must be reduced for safety, but this compromises obliteration. In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to symptomatic AVMs >15 ml in volume.

METHODS:

During a 17-year interval at the University of Pittsburgh, 1040 patients underwent radiosurgery for a brain AVM. Out of 135 patients who had multiple procedures, 37 patients underwent prospectively staged volume radiosurgery for symptomatic otherwise unmanageable larger malformations. Twenty-eight patients who were managed before 2002 were included in this study to achieve sufficient follow-up in assessing the outcomes. The median age was 37 years (range, 13–57 yr). Thirteen patients had previous hemorrhages and 13 patients had attempted embolization. Separate anatomic volumes were irradiated at 3 to 8 months (median, 5 mo) intervals. The median initial AVM volume was 24.9 ml (range, 10.2–57.7 ml). Twenty-six patients had two stages and two had three-stage radiosurgery. Seven patients had repeat radiosurgery after a median interval of 63 months. The median target volume was 12.3 ml. (range, 4.2–20.8 ml.) at Stage I and 11.5 ml. (range, 2.8–22 ml.) at Stage II. The median margin dose was 16 Gy at both stages. Median follow-up after the last stage of radiosurgery was 50 months (range, 3–159 mo).

RESULTS:

Four patients (14%) sustained a hemorrhage after radiosurgery; two died and two patients recovered with mild permanent neurological deficits. Worsened neurological deficits developed in one patient. Seizure control was improved in three patients, was stable in eight patients and worsened in two. Magnetic resonance imaging showed T2 prolongation in four patients (14%). Out of 28 patients, 21 had follow-up more than 36 months. Out of 21 patients, seven underwent repeat radiosurgery and none of them had enough follow- up. Of 14 patients followed for more than 36 months, seven (50%) had total, four (29%) near total, and three (21%) had moderate AVM obliteration.

CONCLUSIONS:

Prospective staged volume radiosurgery provided imaging defined volumetric reduction or closure in a series of large AVMs unsuitable for any other therapy. After 5 years, this early experience suggests that AVM related symptoms can be stabilized and anticipated bleed rates can be reduced.
Gamma-Knife Radiosurgery for Cranial Base Meningiomas: Experience of Tumor Control, Clinical Course, and Morbidity in a Follow-Up of More than 8 Years
Authors: Zachenhofer Iris , Wolfsberger Stefan , Aichholzer Martin , Bertalanffy Alexander , Roessler Karl , Kitz Klaus , Knosp Engelbert
Published: December 2005

OBJECTIVE:

Surgical resection of cranial base meningiomas is often limited owing to involvement of crucial neural structures. Within the last 2 decades Gamma Knife radiosurgery (GKRS) has gained increasing importance as an adjunct treatment after incomplete resection and as an alternative treatment to open surgery. However, reports of long-term results are still sparse. We therefore performed this study to analyze the long-term results of GKRS treatment of cranial base meningiomas, following our previously published early follow-up experience.

METHODS:

A retrospective analysis of the medical files for Gamma Knife and surgical treatments, clinicoradiological findings, and outcome was carried out focusing on tumor control, clinical course, and morbidity.

RESULTS:

Between 1992 and 1995, we treated 36 patients with cranial base meningiomas using GKRS (male:female ratio, 1:5; mean age, 59 yr; range, 44–89 yr). Twenty-five patients were treated with GKRS after open surgery, and 11 patients received GKRS alone. Tumor control, neurological outcomes, and adverse effects were analyzed after a long-term follow-up period (mean, 103 mo; range, 70–133 mo) and compared with our previous results after an early follow-up period (mean, 48 mo; range, 36–76 mo). Control of tumor growth was achieved in 94% of patients. Compared with the early follow-up period, the late neuroradiological effects of GKRS on cranial base meningiomas were continuing tumor shrinkage in 11 patients (33%), stable tumor size in 20 patients (64%) and tumor progression in two meningiomas (6%). The neurological status improved in 16 patients (44%), remained stable in 19 patients (52%), and deteriorated in one patient (4%). Adverse side effects of GKRS were found only during the early follow-up period.

CONCLUSION:

Our data confirm that GKRS is not only a safe and effective treatment modality for cranial base meningiomas in short-term observation, but also in a mean long-term follow-up period of more than 8 years. Tumor shrinkage and clinical improvement also continued during the longer follow-up period.
Brainstem Metastases: Management Using Gamma Knife Radiosurgery
Authors: Fuentes Stéphane , Delsanti Christine , Metellus Philippe , Peragut Jean Claude , Grisoli François , Regis Jean
Published: December 2005

OBJECTIVE:

Brainstem metastasis is an uncommon complication of systemic cancer, generally considered to have a highly unfavorable prognosis. Surgical risks are high and standard radiation or chemotherapy have little effect. The purpose of this study is to evaluate our experience using Gamma Knife radiosurgery (GKRS) for the management of brainstem metastasis.

METHODS:

Between July 1992 and March 2001, we treated 28 patients with brainstem metastasis using GKRS. Lesions were located in the pons in 17 patients, midbrain in nine, and medulla oblongata in two. At time of the radiosurgery, eight patients presented with another supratentorial metastasis. The most frequent primary tumor site was the lung (13 cases) followed by the melanoma in four cases, the kidney in two, and other locations in six. Only six patients underwent fractionated whole-brain radiation therapy. Mean marginal radiation dose for GKRS was 19.6 Gy (range, 11–30). Mean maximum diameter was 17.2 mm (range, 10–30).

RESULTS:

No GKRS-related morbidity was observed. Local tumor control was achieved in 92% of patients. Twenty-six patients have died. Death was related to the progression of the brainstem lesion in two cases. Mean and median survival after GKRS were 10.2 and 12 months, respectively. Follow-up periods in the two surviving patients were 12 and 13 months.

CONCLUSION:

The results of this small series demonstrate that GKRS can be a valuable modality for safe and effective management of brain stem metastasis. Owing to the high risk of surgical resection and low efficacy of medical treatment, radiosurgery can be proposed upfront.
Revascularization and Parent Artery Occlusion for Giant Internal Carotid Artery Aneurysms in the Intracavernous Portion Using Intraoperative Monitoring of Cerebral Hemodynamics
Authors: Kubo Yoshitaka , Ogasawara Kuniaki , Tomitsuka Nobuhiko , Otawara Yasunari , Kakino Shunsuke , Ogawa Akira
Published: December 2005

OBJECTIVE:

Therapeutic parent artery occlusion with or without revascularization is a useful surgical technique for the management of a giant aneurysm located in the intracavernous portion of the internal carotid artery (ICA). The purpose of the present study was to determine whether intraoperative cortical blood flow (CoBF) monitoring during surgical parent artery occlusion could identify patients who required bypass with a saphenous vein graft (high flow bypass).

METHODS:

Eleven patients with a giant aneurysm located in the intracavernous portion of the ICA underwent superficial temporal artery-middle cerebral artery bypass. CoBF was monitored intraoperatively in all patients using a thermal diffusion flow probe. The lowest CoBF during test occlusion of the ICA under functioning superficial temporal artery-middle cerebral artery bypass was determined, and the ratio of the value to the CoBF immediately before test occlusion of the ICA was calculated in the frontal and temporal lobes. When the CoBF ratio in the frontal or temporal lobe was less than 0.9, high flow bypass grafting was elected.

RESULTS:

Of the eleven patients undergoing superficial temporal artery-middle cerebral artery bypass, five patients underwent concomitant high flow bypass grafting. Postoperative cerebral ischemic events did not occur in any patient over a follow-up period ranging from 3 to 60 months. Postoperative cerebral angiography showed resolution of the aneurysm and patency of the bypass in all patients.

CONCLUSION:

Intraoperative CoBF monitoring using a thermal diffusion flow probe during surgical parent artery occlusion for giant intracavernous carotid artery aneurysms can identify patients who require concomitant high flow bypass grafting.
High Dose Magnesium Infusions Are Not Associated with Increased Pressor Requirements after Carotid Endarterectomy
Authors: Chiu Camay , Heyer Eric J. , Rampersad Anita D. , Zurica Joseph , Ornstein Eugene , Sahlein Daniel H. , Sciacca Robert R. , Connolly E Sander
Published: December 2005

INTRODUCTION:

Although magnesium provides cerebral protection in animal stroke models, magnesium therapy has significant side effects in humans. Therefore, we sought to examine the incidence of α-agonist treated hypotension in our ongoing, prospective, randomized, double-blind, placebo-controlled Phase I/IIa dose escalation study of magnesium therapy in patients undergoing carotid endarterectomy.

METHODS:

Eighty patients undergoing elective carotid endarterectomy were randomly assigned to a placebo control group (n = 38) or to one of the three intravenous magnesium groups. Magnesium levels were obtained before induction, and then 15 minutes, 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after a loading dose and infusion. After surgery, a target systolic blood pressure range was chosen, and the amount and duration of phenylephrine needed to maintain that pressure was compared across treatment groups.

RESULTS:

All treatment groups achieved levels significantly different from baseline at 12 and 24 hours (P<0.01). Magnesium treatment did not significantly increase the proportion of patients requiring pressure support. For those requiring pressure support, the amount and average duration of phenylephrine required was not different between control patients and those receiving magnesium, even when the individual minimum systolic blood pressures required were subdivided on the basis of dose of magnesium administered.

CONCLUSION:

There were no significant differences detected in the 1) percentage of patients requiring pressor support, 2) the duration of postoperative pressor support, or 3) the amount of phenylephrine support needed between controls and magnesium treated patients. The percentage of patients requiring pressure support depended on the minimum systolic blood pressure ordered after surgery.
Spinal Neurenteric Cysts in the Magnetic Resonance Imaging Era
Authors: Menezes Arnold H. , Traynelis Vincent C.
Published: December 2005

OBJECTIVE:

Neurenteric cysts are derived from displaced entodermal tissue. They are infrequently found in the ventral spinal canal with varying degrees of success in their removal. Experience with 10 such individuals is critically analyzed to aid in the diagnosis and management.

METHODS:

Ten patients, ages 4 through 55 years, with neurenteric cysts were encountered in the last 20 years. This series included three females and seven males; seven children and three adults. The follow-up periods ranged from 3 to 18 years. Three cysts were located at the ventral cervicomedullary junction, five in the midventral cervical spine, and one thoracic and one lumbosacral. The symptoms reflected the location.

RESULTS:

Six of the 10 patients had associated bony abnormalities such as bifid clivus, hemivertebrae, segmentation failures at the site of the lesion, and blocked vertebra. The patient with the thoracic spinal lesion (age, 55 yr) had symptoms from early childhood. A diplomyelia at the site of the lesion was seen in one individual and tethered spinal cord in the same adult and in a young child. Two patients had undergone laminectomy for aspiration and partial resection before referral to our institution at the time of recurrence. Cervicomedullary junction lesions were approached via the far lateral transcondylar approach; two of the cervical intramedullary lesions were resected via a ventral corpectomy with radical resection and interbody fusion. The goal in each case was complete resection to avoid recurrences.

CONCLUSION:

Spinal neurenteric cysts are ventrally located, usually intradural and extramedullary, but may insinuate into the spinal cord. They are isointense on T1 images and hyperintense on T2-weighted images on magnetic resonance imaging without true enhancement. These lesions may be associated with block and hemivertebrae with a predisposition to the craniocervical region. Partial resections have led to recurrence and arachnoiditis.
Analysis of Pain Resolution after Surgical Resection of Intramedullary Spinal Cord Cavernous Malformations
Authors: Kim Louis J. , Klopfenstein Jeffrey D. , Zabramski Joseph M. , Sonntag Volker K.H. , Spetzler Robert F.
Published: December 2005

OBJECTIVE:

To determine the short- and long-term effects of surgical resection of intramedullary spinal cavernous malformations on preoperative pain.

METHODS:

Between 1988 and 2003, 53 intramedullary spinal cavernous malformations were surgically managed. A retrospective analysis of this cohort revealed 23 (43%) patients who presented with pain as a clinically relevant feature. Long-term evaluation of pain outcomes was available in 21 patients. Pain outcomes were characterized as improved, unchanged, or worse compared with preoperative and immediate postoperative status.

RESULTS:

Seven patients presented with radiculopathy, 12 with central pain, and four with both. Immediately after surgery, pain symptoms improved in 18 (78%) patients, were unchanged in 5 (22%), and were worse in none compared with the patients' preoperative status (n = 23). During the follow-up period, 11 (52%) patients improved, nine (43%) remained at their preoperative baseline, and one (5%) was worse compared with their preoperative levels of pain. The difference in postoperative and long-term pain status was statistically significant (P = 0.031).

CONCLUSION:

The surgical efficacy for improving pain related to intramedullary spinal cavernous malformations may be worse than implied in the literature. Although pain relief immediately after surgery is good, we found that recurrence is common and that only approximately 50% of patients report long-term benefit. Despite the significant limitations of this retrospective study, these data may serve as a guide when counseling patients preoperatively to help them to maintain realistic expectations about outcomes.
Peripheral Neurostimulation for Treatment of Intractable Occipital Neuralgia
Authors: Slavin Konstantin V. , Nersesyan Hrachya , Wess Christian
Published: December 2005

OBJECTIVE:

Medically intractable pain caused by occipital neuralgia (ON) can be very difficult to control with traditional pain management. Peripheral nerve stimulation (PNS) may serve as a good alternative to destructive surgical manipulations used currently for the treatment of severe ON.

METHODS:

We analyzed records of 14 consecutive patients (9 women and 5 men; mean age, 43.3 yr) with intractable ON treated with PNS during the period from April 2002 to November 2004. Five patients had unilateral and nine had bilateral PNS electrodes inserted for trial, which was considered successful if patient reported at least 50% decrease of pain on the visual analogue scale. Ten patients proceeded with system internalization, and their long-term results were analyzed.

RESULTS:

At the time of the last follow-up examination (5–32 mo, mean 22 mo), seven patients (70%) with implanted PNS systems continue to experience beneficial effects of stimulation, including adequate pain control, continuous employment, and decrease in oral pain medications intake. Two patients had their systems explanted because of loss of stimulation effect or significant improvement of pain, and one patient had part of his hardware removed because of infection.

CONCLUSION:

Overall, the beneficial effect from chronic stimulation in our series persisted in more than half of the patients for whom procedure was considered and in 80% of those who significantly improved during the trial and proceeded with internalization. Thus, chronic PNS may be a safe and relatively effective method for long-term treatment of chronic pain syndrome in patients with medically intractable ON.
Radiographic Characteristics Fail to Predict Clinical Course after Subdural Electrode Placement
Authors: Mocco J , Komotar Ricardo J. , Ladouceur Amos K. , Zacharia Brad E. , Goodman Robert R. , McKhann Guy M.
Published: December 2005

OBJECTIVE:

Subdural arrays of grid and strip electrodes are frequently used in epilepsy patients to localize the seizure focus and determine the location of critical brain functions via stimulation mapping. Postoperatively, the majority of patients with implanted subdural electrodes develop subacute extra-axial collections (EACs). Although conservative management is appropriate in most of these cases, occasionally patients manifest neurological symptoms that may necessitate reoperation for collection evacuation. Currently, there is little information available regarding the range of EAC size and the potential correlation between EAC size and symptom development. To facilitate treatment decision-making in postoperative subdural electrode patients, we reviewed and compared the computed tomographic (CT) features of postelectrode placement EACs in asymptomatic and symptomatic patients.

METHODS:

We retrospectively reviewed the medical records and CT scans of 22 consecutive patients who underwent craniotomy for placement of subdural grid and strip electrodes at Columbia University Medical Center. Medical records were reviewed for neurological complications from the time of grid placement until its removal. Each EAC was measured on CT for volume (% of total cranial volume), maximal thickness, and midline shift. One patient was excluded secondary to the development of an intracerebral hemorrhage.

RESULTS:

Thirteen of 21 patients remained asymptomatic or minimally symptomatic during their hospitalization, with only mild to moderate, intermittent, postoperative headaches. The remaining eight developed symptoms such as persistent and severe headache, transient motor deficit, or speech impairment. Two of these patients underwent reoperation for hematoma evacuation. EACs in asymptomatic patients had a mean volume, maximal thickness, and midline shift of 5.7%, 1.25 cm, and 0.33 cm, respectively. EACs in symptomatic patients had a mean volume, maximal thickness, and midline shift of 7.7%, 1.46 cm, and 0.5 cm, respectively. Differences between maximal thickness and midline shift did not approach statistical significance. Despite this, the difference between the mean volume of symptomatic and asymptomatic EACs was statistically significant (P = 0.04).

CONCLUSION:

The conventional methods of midline shift and maximal thickness for assessing EAC size did not adequately differentiate symptomatic and asymptomatic subdural electrode patients with EACs. Although total volume calculation using digital planimetric analysis demonstrated a statistically significant difference, we found no clear threshold volume that correlated with clinical course. Therefore, the appearance of EACs on CT scans is of limited use in predicting the development of symptoms and possible postoperative complications after subdural grid placement. Clinical judgment must guide management and determine the potential need for reoperation.
The Motor Thalamus in Neurosurgery
Authors: Hamani Clement , Dostrovsky Jonathan O. , Lozano Andres M.
Published: December 2005

THE MOTOR THALAMUS is an important target for the treatment of tremor. It receives afferents from the cerebellum, globus pallidus internus, and substantia nigra and projects mainly to the motor cortex, premotor cortex, and supplementary motor area. Various nomenclatures have been proposed to subdivide the motor thalamus, none of which are universally accepted. Both thalamic lesions and high-frequency stimulation ameliorate tremor in diverse pathological conditions. Modern neurophysiological techniques have allowed the recording of the activity of thalamic neurons in patients with different clinical conditions. This has provided a better understanding of the functions of the motor thalamus in humans. The aim of the present article is to briefly review the major anatomic and physiological aspects of the motor thalamus as well as the electrophysiological findings described in humans undergoing surgical procedures.
Expression of Integrins in Cerebral Arteriovenous and Cavernous Malformations
Authors: Seker Aşkın , Yildirim Özlem , Kurtkaya Özlem , Sav Aydin , Günel Murat , Pamir M Necmettin , Kılıç Türker
Published: December 2005

OBJECTIVE:

To assess and compare levels and patterns of expression for integrins αvβ1, αvβ3, and αvβ5 in arteriovenous malformations (AVMs) and cavernous malformations (CCMs) of the brain.

MATERIALS AND METHODS:

Specimens from 10 AVM and 10 CCM lesions were selected from 112 patients with AVMs and 97 patients with CCMs who were treated microsurgically in the Department of Neurosurgery, Marmara University, Istanbul, Turkey. Sections were immunohistochemically stained with antibodies for integrins αvβ1, αvβ3, and αvβ5. Separate histological layers of the vascular wall were evaluated, and levels of expression were graded using a four-tier system.

RESULTS:

Integrin αvβ1 was more strongly expressed in AVMs than in CCMs. This difference was most pronounced in the endothelium and subendothelium/media. Integrin αvβ3 was more strongly expressed in CCM endothelium than in AVM endothelium (average grades, 0.9 and 0.4, respectively). All 10 of the CCM lesions expressed integrin αvβ5 in the endothelium, whereas only five of the AVMs showed minimal expression of this molecule in the endothelium.

CONCLUSION:

Current scientific understanding of the roles integrins play in angiogenesis is far from complete. The levels and patterns of expression for these molecules in the histological layers of the vascular walls of AVMs and CCMs provide some clues about the complex biological activities of integrins in these lesions. If one accepts the premise that immunohistochemistry has its inherent methodological problems, integrins αvβ1, αvβ3, and αvβ5 are expressed in AVMs and CCMs in different ways that may be linked to stages of angiogenic maturation. Integrin αvβ1 is expressed more strongly in endothelium and subendothelium/media of AVMs than in the corresponding layers of CCMs. Integrins αvβ3 and αvβ5 are expressed more strongly in CCM endothelium than in AVM endothelium. In addition, integrin αvβ5 staining was stronger in CCM subendothelium than AVM subendothelium/media.
Traumatic Leptomeningeal Cyst in a 24-Year-Old Man: Case Report
Authors: Houra Karlo , Beros Vili , Sajko Tomislav , Cupic Hrvoje
Published: December 2005

OBJECTIVE AND IMPORTANCE:

Traumatic leptomeningeal cysts represent a rare complication of a childhood cranial fracture, and occur in only 0.05 to 0.6% of all cranial fractures. In adults, clinical manifestations of a childhood trauma are very rare and usually appear in the form of nontender, nonpulsatile, subcutaneous mass, accompanied by a progressive neurological deficit and seizures, as shown in our case.

CLINICAL PRESENTATION:

We present the case of a 24-year-old man with seizures caused by a traumatic leptomeningeal cyst resulting from the head injury he suffered at the age of 9 months.

INTERVENTION:

Right-sided craniotomy was performed with consequent microsurgical removal of the leptomeningeal cyst. The dura was reconstructed in a watertight manner and a cranioplasty was performed with Palacos (Howmedica International, Limerick, Ireland).

CONCLUSION:

It is important to consider traumatic leptomeningeal cysts when treating adult patients with erosive bone lesions who have a history of head trauma.
Resolution of Hemifacial Spasm after Surgical Obliteration of a Tentorial Arteriovenous Fistula: Case Report
Authors: Deshmukh Vivek R. , Maughan Peter H. , Spetzler Robert F.
Published: December 2005

OBJECTIVE AND IMPORTANCE:

We describe a patient with a tentorial dural arteriovenous fistula who presented with ipsilateral hemifacial spasm.

CLINICAL PRESENTATION:

A 50-year-old man sought treatment for left facial twitching that worsened over 6 months. Magnetic resonance imaging and catheter angiography demonstrated a left tentorial dural arteriovenous fistula.

INTERVENTION:

The patient underwent a retrosigmoid craniotomy and ligation of the draining vein at the site of the fistula. Intraoperative angiography showed complete obliteration of the fistula. The patient's hemifacial spasm improved significantly after the fistula was obliterated.

CONCLUSION:

Posterior fossa arteriovenous fistulas can present with a hemifacial spasm related to compression of the facial nerve by arterialized leptomeningeal veins. Microsurgical obliteration of the fistula can resolve the related symptoms.
Unrecognized Intracerebral Glass Particle Mimicking Cavernoma: Case Report
Authors: Inci Servet , Karakoc Ebru , Saygi Serap , Ozgen Tuncalp
Published: December 2005

OBJECTIVE AND IMPORTANCE:

Although the presence of a foreign body in the cranium after a head injury is a well-known entity, cases of retained intracranial foreign bodies causing a delayed onset of neurological symptoms are rare. To our knowledge, an unrecognized intracerebral glass particle mimicking a cavernoma has not been previously reported in the literature.

CLINICAL PRESENTATION:

We report a unique case regarding an intracranial foreign body. A 39-year-old patient presented with new-onset epilepsy. The patient had no history of trauma. According to the magnetic resonance imaging findings and the patient's clinical course, the responsible lesion was considered to be a temporal cavernoma.

INTERVENTION:

During the operation, surprisingly, a glass particle was found within the temporal lobe. The glass had penetrated the cranium during a minor head injury and had remained undetected for 33 years. The patient was seizure-free without medication during 3 years of follow-up.

CONCLUSION:

Intracranial small foreign bodies can be difficult to diagnose, especially in patients with no history or a vague history of head trauma. Patients with long-standing retained foreign bodies may remain clinically well until complications arise. Intracranial foreign bodies may mimic other pathologies clinically and radiologically.
Repeat Endovascular Treatment in Post-Embolization Recurrent Intracranial Aneurysms
Authors: Kang Hyun-Seung , Han Moon Hee , Kwon Bae Ju , Kwon O-Ki , Kim Sung Hyun
Published: December 2005

OBJECTIVE:

The purpose of this study was to describe clinical situations requiring repeat embolization in patients previously treated by endovascular coil embolization for intracranial aneurysms, and to report on our experiences of repeat embolization (RE).

METHODS:

A total of 466 patients harboring 522 intracranial aneurysms were treated by endovascular coil embolization at our institution during the period between December 1992 and August 2004. We studied 32 patients who underwent repeat coil embolization (RE) owing to recanalization or aneurysm recurrence. Radiological and clinical data were reviewed to determine the reasons, results, and technical problems of RE.

RESULTS:

Thirty-nine sessions of RE were performed in 32 patients; four patients underwent RE twice and another patient three times. The major reason for RE was asymptomatic aneurysmal recanalization owing to coil compaction and/or loosening. The time interval between RE and the previous embolization was 12 months or less in 27 sessions. Complete or near complete occlusion of the aneurysm was achieved in all cases without procedure-related morbidity or mortality. Radiolucent gaps between the coil masses were observed in 17 cases.

CONCLUSION:

RE is a safe and effective treatment option in cases of recanalized or recurrent aneurysms. Close follow-up evaluation is essential in patients with intracranial aneurysms after coil embolization.
Durability of Aneurysm Embolization with Matrix Detachable Coils
Authors: Fiorella David , Albuquerque Felipe C. , McDougall Cameron G.
Published: December 2005

OBJECTIVE:

Matrix detachable coils (MDC; Boston Scientific/Target, Fremont, CA) are platinum coils coated with a bioabsorbable polymeric material (polyglycolic-polylactic acid). In animal models, the introduction of polyglycolic-polylactic acid-coated coils into experimental aneurysms resulted in a cellular reaction which promoted stable intra-aneurysmal scar tissue formation. The current study was undertaken to assess the durability of aneurysm occlusion after embolization with MDC.

METHODS:

All patients undergoing embolization were prospectively enrolled in an endovascular database at our institution. All coils used for embolization were recorded in the operative notes for the procedure. Only aneurysms embolized with 50% or greater length of MDC were included. All patients with Neuroform stents (Boston Scientific/Target, Fremont, CA) were excluded from the study. Patients were followed with conventional angiography and magnetic resonance angiography.

RESULTS:

During a 20-month period, 131 aneurysms were embolized with MDC. Follow up data (average, 6.9 mo; range, 1.5–22 mo) were available for 82 aneurysms (61 with conventional angiography, 21 with magnetic resonance angiography only). Of the aneurysm patients with follow-up available, 65 had small aneurysms with small necks, three were small aneurysms with wide necks, 12 were large aneurysms, and two were giant aneurysms. Overall, there were 30 (36.6%) recanalizations, 19 (23.1%) of which required retreatment. In two additional patients, retreatment was either recommended (n = 1) or attempted unsuccessfully (n = 1). Fifty–two aneurysms were unchanged or demonstrated progressive thrombosis (63.4%). The recanalization rate for small aneurysms with small necks was 26.1% (17 out of 65) with a 13.8% retreatment rate (9/65). The recanalization rate for large aneurysms was 75% (9 out of 12) with seven requiring retreatment.

CONCLUSION:

In the absence of Neuroform stent support, aneurysms embolized with the MDC system demonstrated a significant rate of recanalization. Many of the recanalizations were of sufficient size to warrant retreatment. The rates of recanalization observed in the present series were comparable to, or worse than, those reported for bare platinum coils.
E-cadherin loss promotes the initiation of squamous cell carcinoma invasion through modulation of integrin-mediated adhesion
Authors: Zhang Weitian , Alt-Holland Addy , Margulis Alexander , Shamis Yulia , Fusenig Norbert E. , Rodeck Ulrich , Garlick Jonathan A.
Published: January 2006

Much remains to be learned about how cell-cell and cell-matrix interactions are coordinated to influence the earliest development of neoplasia. We used novel 3D human tissue reconstructs that mimic premalignant disease in normal epidermis, to directly investigate how loss of E-cadherin function directs conversion to malignant disease. We used a genetically tagged variant of Ha-Ras-transformed human keratinocytes (II-4) expressing dominant-interfering E-cadherin fusion protein (H-2kd-Ecad). These cells were admixed with normal human keratinocytes and tumor cell fate was monitored in 3D reconstructed epidermis upon transplantation to immunodeficient mice. Tumor initiation was suppressed in tissues harboring control- and mock-infected II-4 cells that lost contact with the stromal interface. By contrast, H-2kd-Ecad-expressing cells persisted at this interface, thus enabling incipient tumor cell invasion upon in vivo transplantation. Loss of intercellular adhesion was linked to elevated cell surface expression of α2, α3 and β1 integrins and increased adhesion to laminin-1 and Types I and IV collagen that was blocked with β1-integrin antibodies, suggesting that invasion was linked to initial II-4 cell attachment at the stromal interface. Collectively, these results outline a novel aspect to loss of E-cadherin function that is linked to the mutually interdependent regulation of cell-cell and cell-matrix adhesion and has significant consequences for the conversion of premalignancy to cancer.
Recommendations for the management of retarded ejaculation: BASHH Special Interest Group for Sexual Dysfunction
Authors: Richardson Daniel , Goldmeier David ,   BASHH Special Interest Group for Sexual Dysfunction
Published: December 2005

We present the British Association of Sexual Health and HIV (BASHH) special interest group in sexual dysfunction recommendations for the management of retarded ejaculation. The recommendations outline the physiology, prevalence, definitions, aetiological factors and patient assessment for this sexual problem. We suggest treatment strategies, recommendations for management and an auditable outcome.
Emergence of quinolone-resistant Neisseria gonorrhoeae in Pakistan
Authors: Jabeen Kauser , Khan Erum , Hasan Rumina
Published: December 2005

Quinolone-resistant Neisseria gonorrhoeae (QRNG) have not been reported from Pakistan to date. This is the first report of the presence of QRNG in Pakistan. The study was performed at a tertiary care hospital laboratory in Karachi, Pakistan. Antimicrobial susceptibility data on all N. gonorrhoeae isolated between 1992 and 2002 were retrieved and analysed. Minimum inhibitory concentrations (MICs) of QRNG isolated in year 2002 were performed, and clinical information was collected. QRNG was first noted in 1999 and its proportion increased to 42% in 2002. MICs of the 12 isolates tested in 2002 showed a high level of resistance to ofloxacin with MIC of more than 4 μg/mL. Clinical information from patients with QRNG showed treatment failure. Emergence of QRNG in developing countries is alarming as there is no proper surveillance of increase in resistance. We strongly urge the need of detection and documentation of the resistant gonococcal isolates, as in vitro resistance is associated with clinical failure.