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Tiffany M Pouldar,1 Dermot P Maher,2 Alexander W Betz,1 Jeffrey J Wiegers,1 Jeremy A Friedman,1 Sameer S Zaidi,1 Ali Rejali,3 Hai P Tran,3 Roya Yumul,1,4 Charles Louy1 1Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; 2Department of Anesthesiology and Critical Care Medicine, Pain Medicine Division, Johns Hopkins Hospital, Baltimore, MD, 21205, USA; 3Department of Pharmacy, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; 4Department of Anesthesiology, David Geffen School of Medicine-UCLA, Los Angeles, CA, 90095, USACorrespondence: Charles Louy, Department of Anesthesiology, Cedars-Sinai Medical Center, 8700 Beverly Blvd #8211, Los Angeles, CA, 90048, USA, Tel +1 310-423-5841, Email CHLOUY@gmail.comObjective: There has been increasing use of ketamine at subanesthetic doses as an adjunct to opioids in perioperative pain management. There are several known adverse drug effects (ADEs) associated with ketamine. However, the incidence of ADEs with ketamine infusions with patient-controlled analgesia (PCA) boluses compared with combined opioid and ketamine PCAs is not well described. The objectives of this study were to compare the incidence and type of ADEs in postoperative spine surgery patients on ketamine infusions with as-needed PCA boluses to patients on combined opioid and ketamine PCAs.Methods: The medical records of patients who underwent spine surgery between March 2016 and March 2020 who were postoperatively treated with a ketamine infusion and as-needed PCA boluses and parenteral opioids or treated with a combined opioid and ketamine PCA were reviewed. Perioperative information including patient characteristics and preoperative morphine equivalent daily dose (MEDD) were collected. Patient charts were reviewed for ADEs including psychological and neurological side effects, nausea, and new-onset tachycardia.Results: A total of 315 patients met the inclusion criteria and were included in the final analysis. Of these patients, 121 experienced at least one ADE (38%). Sixteen of the 68 ketamine infusion with PCA bolus patients (24%), 77 of the 203 hydromorphone and ketamine patients (38%), and 28 of the 44 morphine and ketamine patients (64%) experienced an ADE [p< 0.01]. In patients with preoperative MEDD ≤ 90, nausea was the only ADE that differed significantly among the three groups.Conclusion: This retrospective analysis suggests that postoperative spine patients treated with a ketamine infusion with as-needed PCA boluses and parenteral opioids were associated with fewer ADEs when compared to an intravenous combined opioid and ketamine PCA. In patients with preoperative MEDD ≤ 90, nausea with and without emesis was the only ADE that showed statistically significant difference amongst the three groups.Keywords: ketamine, opioid, patient-controlled analgesia, adverse drug effects, postoperative, retrospective

BACKGROUND: Sjogren's syndrome (SS) is a common autoimmune disorder in which liver involvement is frequent, but generally mild and subclinical. Multiple hepatic histologies have been reported, but to our knowledge an association with granulomatous hepatitis (GH) has never been described. We recently evaluated an individual in whom biopsy-proven GH was associated with concomitant SS. OBJECTIVE: To clarify the possible association between GH and SS. METHODS: We retrospectively reviewed all cases of biopsy-proven GH seen in our institution from 1991 to 2004. Overall, there were 16 individuals with GH identified of which 4 were considered idiopathic in origin. These individuals underwent an extensive evaluation for the presence of SS as well as other disorders known to be associated with GH. RESULTS: Of the 4 identified cases with a previously suspected idiopathic GH, 3 met criteria for primary SS. All 3 individuals underwent minor salivary gland biopsy, which was diagnostic for this condition. CONCLUSIONS: These results suggest a likely association between these 2 conditions. Further epidemiological studies will be necessary to confirm this finding. Copyright © 2006 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Abstract Background To examine the natural growth dynamics of internal plexiform neurofibromas (PNs) in patients with neurofibromatosis 1 (NF1). Methods Two hundred and one NF1 patients underwent whole body MRI (WBMRI). Tumour burden was estimated volumetrically. Non-parametric Spearman’s rho correlation coefficients were used to analyse the relationship of growth rate to tumour volume and age. Chi-squared and Mann–Whitney U tests were used for analysing the association of tumour occurrence with sex or age. Chi-squared tests were used to analyse the association of tumour growth with age group. Results Seventy-one of 171 patients with serial WBMRI exams had internal PNs (median follow up 2.2 years [1.1 to 4.9 years]). Median whole body tumour volume was 86.4 mL [5.2 to 5878.5 mL]) with a median growth rate of 3.7%/year (−13.4 to 111%/year) that correlated with larger whole body tumour volume (PP=0.004). No new PNs developed in 273.0 patient-years among patients without tumours. Rate of new tumour development among patients with PNs was 0.6%/year (95% confidence interval 0.02 to 3.4%). Twenty-seven (13.5%) tumours increased significantly and were more frequent among children (PP Conclusion Children with NF1 and internal PNs are at risk for tumour growth. Most PNs grow slowly or not at all, and some decrease in size. New tumours are infrequent in NF1 patients with PNs and unlikely in patients without PNs.

Abstract Background Clinical laboratories are adopting array genomic hybridization as a standard clinical test. A number of whole genome array genomic hybridization platforms are available, but little is known about their comparative performance in a clinical context. Methods We studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500 K GeneChip SNP arrays, Agilent Human Genome 244 K oligonucleotide arrays and NimbleGen 385 K Whole-Genome oligonucleotide arrays. We also determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32 K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP arrays. Results The Affymetrix 500 K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosomal CNVs in the 30 trios. 147 of these CNVs appeared to be de novo, but only 34 (22%) were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 most likely pathogenic and 2 possibly pathogenic CNVs for MR. All 9 of these putatively pathogenic CNVs were detected by the Affymetrix 500 K, Agilent, NimbleGen and the Illumina arrays, and 5 were found by the SMRT BAC array. Both putatively pathogenic CNVs identified in the 15 trios tested with the Affymetrix 6.0 were identified by this platform. Conclusions Our findings demonstrate that different results are obtained with different platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls on each of the platforms supports the need for validating clinically important findings with a different technology.

Purpose: The purpose of this study was to determine the association between lens thickness and cataract in participants aged 0 to 5 years., Design: This was a prospective, multicenter, case-control study., Participants: We enrolled 118 participants (171 eyes) aged 0 to 5 years, mean age 14.6 ± 17.0 months, range 0 to 60 months., Methods: Lens thickness was measured on 342 ultrasound biomicroscopy (UBM) images., Main Outcome Measures: Lens thickness; feasibility of lens thickness measurement from UBM images., Results: The mean lens thickness among noncataracts was 3.60 ± 0.17 mm, compared with 3.16 ± 0.61 mm among cataracts ( P < 0.0001). Lens thickness <3.5 mm was significantly associated with increased odds of cataract; adjusted odds ratio = 5.99 (95% confidence interval, 2.41-14.88; P < 0.0003) among participants age 0 to 7 months. Lens thickness was significantly associated with cataract laterality among participants age 0 to 7 months ( P < 0.0001)., Conclusions: Quantitative UBM can be used to evaluate lens thickness in infants and children with congenital cataracts. The lens in congenital cataract eyes was thinner than that of controls among infants. Abnormal lens thickness was significantly associated with cataract. Future longitudinal studies will examine the association between lens thickness and postcataract surgery outcomes., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Left ventricular assist device-destination therapy (LVAD-DT) represents a powerful technology capable of prolonging and significantly altering recipients' lives. The objective of this systematic review is to analyze the experiences of LVAD-DT recipients and recommend directions of further study. This is a qualitative research project; a systematic review, using thematic meta-synthesis. Six studies were reviewed. Three over-arching themes supported by seven conceptual categories were recognized across the six studies. The three overarching themes are that LVAD-DT recipients continue to struggle with complex support needs post implantation; the motivations for accepting LVAD-DT is death avoidance, and symptom relief; and, that recipients often believe the device will reverse or fix their heart failure. Although elemental, these themes suggest LVAD-DT recipients' interests may not be well served by the informed consent process. The number of LVAD-DT recipients continues to grow and age, presenting significant implications for healthcare providers as a result of this finding., Competing Interests: Declaration of Competing Interest The author has no conflicts. This research did not receive any specific grant from agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Submucosal uterine leiomyomas are a common benign pelvic tumor that can cause abnormal uterine bleeding and may contribute to infertility and miscarriage. Hysteroscopic myomectomy is the treatment of choice to alleviate bleeding from these myomas and to normalize the uterine cavity. This review discusses the techniques and recent evidence for hysteroscopic myomectomy and examines the two primary surgical tools employed today: the bipolar resectoscope and hysteroscopic mechanical morcellator., Recent Findings: Hysteroscopic myomectomy has been a popular treatment for symptomatic submucosal fibroids for decades; it is a minimally invasive, low-cost, low-risk procedure, and is associated with high patient satisfaction. There have been rapid advances in the surgical technology available for this procedure. Both the bipolar resectoscope and the hysteroscopic mechanical morcellator are appropriate tools to remove submucosal myomas. Although the hysteroscopic morcellators have been associated with shortened operative time and a decreased learning curve, the data are limited for their use on type 2 fibroids. The strength of the bipolar resectoscope lies in its ability to resect deeper type 2 fibroids., Summary: The evidence suggests that no one technique should be used for all patients, but rather a choice of technique should be taken on a case-by-case basis, depending on the myoma number, size, type, and location. Gynecologists must become knowledgeable about each of these techniques and their associated risks to safely offer these surgeries to their patients.

Trisomy and triploidy, defined as the presence of a third copy of one or all chromosomes, respectively, are deleterious in many species including humans. Previous studies have demonstrated that Caenorhabditis elegans with a third copy of the X chromosome are viable and fertile. However, the extra X chromosome was shown to preferentially segregate into the first polar body during oocyte meiosis to produce a higher frequency of euploid offspring than would be generated by random segregation. Here, we demonstrate that extra autosomes are preferentially eliminated by triploid C. elegans and trisomy IV C. elegans Live imaging of anaphase-lagging chromosomes and analysis of REC-8 staining of metaphase II spindles revealed that, in triploids, some univalent chromosomes do not lose cohesion and preferentially segregate intact into the first polar body during anaphase I, whereas other autosomes segregate chromatids equationally at anaphase I and eliminate some of the resulting single chromatids during anaphase II. We also demonstrate asymmetry in the anaphase spindle, which may contribute to the asymmetric segregation. This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency., (Copyright © 2017 by the Genetics Society of America.)

Heat shock protein 90 (HSP90) is a chaperone protein that stabilizes proteins involved in oncogenic and therapeutic resistance pathways of epithelial cancers, including head and neck squamous cell carcinomas (HNSCCs). Here, we characterized the molecular, cellular, and preclinical activity of HSP90 inhibitor SNX5422/2112 in HNSCC overexpressing HSP90. SNX2112 inhibited proliferation, induced G2/M block, and enhanced cytotoxicity, chemosensitivity, and radiosensitivity between 25 and 250 nM in vitro. SNX2112 showed combinatorial activity with paclitaxel in wild-type (wt) TP53-deficient and cisplatin in mutant (mt) TP53 HNSCC lines. SNX2112 decreased expression or phosphorylation of epidermal growth factor receptor (EGFR), c-MET, v-akt murine thymoma viral oncogene homolog 1 (AKT), extracellular signal-regulated kinases (ERK) 1 and 2, inhibitor κB kinase, and signal transducer and transcription factor 3 (STAT3), corresponding downstream nuclear factor κB, activator protein-1, and STAT3 reporter genes, and target oncogenes and angiogenic cytokines. Furthermore, SNX2112 enhanced re-expression of TP53 and targets p21WAF1 and PUMA, while TP53 inhibitor Pifithrin or siRNA attenuated the antiproliferative activity of SNX2112 in wtTP53 HNSCC in vitro. Prodrug SNX5422 similarly down-modulated key signal targets, enhanced TP53 expression and apoptosis, and inhibited proliferation, angiogenesis, and tumorigenesis in a wtTP53-deficient HNSCC xenograft model. Thus, HSP90 inhibitor SNX5422/2112 broadly modulates multiple key nodes within the dysregulated signaling network, with corresponding effects upon the malignant phenotype. Our data support investigation of SNX5422/2112 in combination with paclitaxel, cisplatin, and radiotherapy in HNSCC with different TP53 status.

Relapsing polychondritis (RP) and familial Mediterranean fever (FMF) are systemic inflammatory disorders with seemingly distinct genetic and pathophysiologic mechanisms. An association between these disorders has been described based on a single case report with few clinical details available. We recently encountered a patient with biopsy-proven RP and genetically confirmed FMF. Following identification of this individual, we conducted a retrospective review of all cases of RP in our institution from 2000-2009 and identified one additional patient with RP who is also a genetic heterozygote for FMF. These cases highlight the previously reported but sparsely documented relationship between these seemingly separate disorders.

Background: The first 24 h in the management of aneurysmal subarachnoid hemorrhage (SAH) represent a critical time period for medical intervention., Methods: We review the current literature and discuss our current clinical practices related to management of acute SAH., Results: A brief objective review of the current evidence along with a subjective overview of the authors practices in the management of aneurysmal subarachnoid hemorrhage in the first 24 h is outlined., Conclusions: The first 24 h following aneurysmal subarachnoid hemorrhage is a critical time period in which medical and interventional management paradigms continue to evolve.

Importance of the Field: Recent advances in the understanding of the oncogenesis of head and neck squamous cell carcinomas (HNSCC) have revealed multiple dysregulated signaling pathways. One frequently altered axis is the EGFR-PI3K-Akt-mTOR pathway. This pathway plays a central role in numerous cellular processes including metabolism, cell growth, apoptosis, survival and differentiation, which ultimately contributes to HNSCC progression., Areas Covered in This Review: Books, journals, databases and websites have been searched to provide a current review on the subject., What the Reader Will Gain: This article reviews the current understanding of EGFR-PI3K-Akt-mTOR signaling in HNSCC, including the impact of both genetic and epigenetic alterations. This review further highlights the potential of targeting this signaling cascade as a promising therapeutic approach in the treatment of HNSCC., Take Home Message: Genetic alterations of several nodes within this pathway, including both genetic and epigenetic changes, leading to either oncogene activation or inactivation of tumor suppressors have frequently been implicated in HNSCC. Consequently, drugs that target the central nodes of this pathway have become attractive for molecular oriented cancer therapies. Numerous preclinical and clinical studies are being performed in HNSCC; however, more studies are still needed to better understand the biology of this pathway.

The authors present a unique case of a patient with communicating hydrocephalus and repeated ventriculoperitoneal shunt obstructions resulting from mucin-secreting enterogenous cell deposits at the cervicomedullary junction. Pathological examinations revealed that these cellular deposits lacked characteristic cystic architecture and the patient had no history of previous cyst with dissemination. Because of the repeated shunt obstructions and inability to surgically resect the lesion in its entirety, the authors elected radiation therapy to the cervicomedullary junction, encompassing the radiological abnormality. As of this writing, the patient has remained at neurological baseline and has not required further shunt revisions for obstruction.

Object: A review of the literature has revealed scant data related to neurosurgical treatment of gravid patients. The authors reviewed their experience with the neurosurgical treatment of pregnant women to better characterize the optimal management strategies for intracranial pathological entities in this population., Methods: Between July 1969 and July 2005, 34 patients with documented pregnancy and concomitant intracranial pathological entities were treated at the authors' institution. The average age of the gravid patients at presentation was 27 +/- 6 years. Twelve patients harbored vascular and 14 patients harbored neoplastic lesions. Four gravid patients suffered from traumatic intracranial hemorrhage, 2 had primary intracerebral hemorrhage, and 2 had hydrocephalus. The medical records of these patients were reviewed to assess the outcome for the mothers and fetuses., Results: Nineteen pregnant patients (56%) underwent a neurosurgical procedure after induction of general anesthesia. Of these, 14 (74%) underwent craniotomies for clipping/resection of their lesion, 2 (10%) underwent stereotactic biopsies, and 3 (16%) underwent CSF shunting procedures. Three patients (9%) delivered by cesarean section followed by their neurosurgical procedure, and 5 (15%) underwent therapeutic abortion preoperatively to allow for radiation therapy early in their pregnancy (4 of these patients underwent surgery prior to their therapeutic abortion). Eleven patients (32%) were treated nonoperatively while pregnant, and 3 of these received their treatment after delivery. There was no operative maternal mortality or permanent morbidity. The fetuses did not suffer from any complications related to the mother's neurosurgical procedure., Conclusions: Based on the authors' experience and a review of the literature, surgery for intracranial lesions in pregnant patients is generally well tolerated by both mother and fetus. Preoperative delivery by cesarean section of term or near-term babies is reasonable. Some patients treated conservatively may deteriorate and require an operation.

We previously demonstrated that there is a significantly greater transfer of intravenously-injected Evan's blue dye into the forebrain of acyclic (reproductive senescent) females compared to young adult females, indicating that blood brain barrier permeability is compromised in the reproductive senescent forebrain. The present study examined brain IgG expression and microvessel tight junction proteins to assess ovarian age-related changes in microvascular permeability, and further compared young and senescent females with age-matched males to distinguish changes attributable to age and reproductive senescence. Blood brain barrier breakdown are often associated with increased extravasation of plasma proteins and high levels of immunoglobulin G (IgG) in brain. In the present study, IgG expression was dramatically increased in the hippocampus and thalamus, but not the hypothalamus of reproductive senescent females compared to young adult females. In males, IgG expression was increased in all these regions in middle-aged animals (aged-matched to senescent females) as compared to young males (age-matched to the young adult females). Furthermore, the proportion of hippocampal microvessels with perivascular IgG immunoreactivity was significantly greater in reproductive senescent females as compared to young adult females, while middle-aged males and young adult males did not differ. The tight junctions between adjacent microvascular endothelial cells regulated by transmembrane proteins such as claudin-5 and occludin play a critical role in maintaining the blood brain barrier integrity. Increased hippocampal IgG expression in senescent females was paralleled by poor junctional localization of the tight junction protein claudin-5 in hippocampal microvessels. However, there was no difference in hippocampal claudin-5 localization between young adult and middle-aged males, indicating that dysregulation of this junctional protein was associated with ovarian aging. Parallel studies in human brain microvessels also revealed age-dependent disruption in claudin-5 distribution in post-menopausal women compared to pre-menopausal women. Collectively, these data support the hypothesis that constitutive loss of barrier integrity in the forebrain during reproductive senescence may be due, in part, to the selective loss of tight junction proteins in endothelial junctions.

Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450mum (n=19) or 660microm in diameter (n=14). Animals were sacrificed after 1, 2 and 3months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450microm scaffolds had significantly greater axon fibers per channel at the 1month (186+/-37) and 3month (78+/-11) endpoints than the 660microm scaffolds (90+/-19 and 40+/-6, respectively) (p=0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660microm channels was most pronounced at the 1month endpoint, at 28,046+/-6551 and 58,633+/-7063microm(2), respectively (p=0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.

Background: Spinal surgery is increasingly being done in the outpatient setting. We reviewed our experience with inpatient and outpatient single-level anterior cervical discectomy and fusion with plating (ACDF+P)., Methods: All patients undergoing single-level anterior cervical discectomy and fusion with plating between August 2005 and May 2007 by two surgeons (RPB or JAF) were retrospectively reviewed. All patients underwent anterior cervical microdiscectomy, arthrodesis using structural allograft, and titanium plating. A planned change from doing ACDF+P on an inpatient basis to doing ACDF+P on an outpatient basis was instituted at the midpoint of the study. There were no other changes in technique, patient selection, instrumentation, facility, or other factors. All procedures were done in full-service hospitals accommodating outpatient and inpatient care., Results: 64 patients underwent ACDF+P as inpatients, while 45 underwent ACDF+P as outpatients. When outpatient surgery was planned, 17 patients were treated as inpatients due to medical comorbidities (14), older age (1), and patient preference (2). At a mean follow-up of 62.4 days, 90 patients had an excellent outcome, 19 patients had a good outcome, and no patients had a fair or poor outcome. There was no significant difference in outcome between inpatients and outpatients. There were 4 complications, all occurring in inpatients: a hematoma one week post-operatively requiring drainage, a cerebrospinal fluid leak treated with lumbar drainage, syncope of unknown etiology, and moderate dysphagia., Conclusion: In this series, outpatient ACDF+P was safe and was not associated with a significant difference in outcome compared with inpatient ACDF+P.

Objectives: Computerized tomographic angiography (CTA) has emerged as a valuable diagnostic tool for the management of patients with cerebrovascular disease. The use of CTA in lieu of, or as an adjunct to, conventional cerebral angiography in the management of cerebral aneurysms awaits further experience. In this study, we evaluated the role of CTA specifically for the pre-operative assessment and planning of cerebral aneurysm surgery., Patients and Methods: We reviewed the relevant neuroimaging of all patients treated at Dartmouth Hitchcock Medical Center between January, 2001 and December, 2004 with a diagnosis of cerebral aneurysm and diagnostic evaluation with both CTA and conventional digital subtraction angiography (DSA) using standard imaging protocols. 32 patients underwent both CTA and DSA during the study period for a total of 36 aneurysms. Images were independently re-assesed by two neurosurgeons for information valuable for pre-operative surgical planning., Results: In 26 of 36 aneurysms (72%), the CTA was felt to provide the best image quality in defining the morphology of the aneurysm. In 14 aneurysms (39%), CTA provided clinically valuable anatomic detail not demonstrated on DSA, largely due to better visualization of parent and perforating vessel relationships at the aneurysm neck. There were no instances where a lesion was seen on DSA but missed on CTA. The DSA was of most clinical value in determining flow dynamics, such as the arterial supply of an anterior communicating artery aneurysm and distal anterior cerebral branches via the two A1 segments., Conclusion: CTA with three-dimensional reconstructions is a valuable adjunct to the preoperative evaluation of cerebral aneurysms. We advocate routine use of CTA in all patients in whom surgical aneurysm repair is planned, even when DSA has already been performed.

Introduction: The reported intracerebral hemorrhage rate due to ventriculostomy placement varies widely. As studies emerge regarding alternative techniques of ventriculostomy placement, and placement by non-neurosurgeons, further definition of the true intracerebral hemorrhage rate associated with ventriculostomy is warranted. We performed a meta-analysis of the existing literature to further elucidate the incidence of intracerebral hemorrhage due to ventriculostomy., Methods: We performed an extensive literature search using Ovid MEDLINE and PubMed for relevant studies published after 1970. Only studies with more than 25 ventriculostomy procedures were included. Data were extracted regarding number of hemorrhages, clinically significant hemorrhages, and the use of routine post-ventriculostomy CT scanning. We performed subgroup analyses based on the use of routine post-ventriculostomy CT scanning. Chi-squared test was used to determine statistical significance., Results: Overall, 102 hemorrhagic complications from 1,790 ventriculostomies were reported, a hemorrhage rate of 5.7%. Of the 102 hemorrhages, 11 were clinically significant (clinically significant hemorrhage rate = 0.61%). In studies that used routine post-placement CT scans, the hemorrhage rate was 10.06%, compared to a hemorrhage rate of 1.53% in studies in which routine CT scans were not performed (P < 0.001). Eight clinically significant hemorrhages (0.91%) were identified in the studies utilizing routine post-procedural CT scanning, compared to three clinically significant hemorrhages (0.33%) in studies without routine CT scans (P = 0.113)., Conclusion: The overall hemorrhage risk associated with ventriculostomy placement based on the existing literature is 5.7%. Clinically significant hemorrhage due to ventriculostomy is less than 1%. Modifications of technique that might reduce hemorrhage risk, and the utility of routine post-procedural CT scanning, merit further investigation.

CT angiography (CTA) is increasingly being utilized in the initial diagnosis of subarachnoid hemorrhage. While active bleeding from an intracranial aneurysm has been demonstrated on conventional angiography, CT angiogram findings of active aneurysmal hemorrhage are not well described. We present a case of an actively bleeding anterior communicating artery aneurysm demonstrated by CT angiography. The initial CTA demonstrated the extravasation of contrast from the anterior communicating artery. A second CT scan less than 1h later confirmed the ongoing hemorrhage, with extension of hemorrhage into the subarachnoid cisterns and the ventricular system. Recognition of active aneurismal hemorrhage by CTA may modify plan of treatment and follow-up imaging.

Introduction: While catheter angiography has traditionally been used to assess the caliber and course of the superficial temporal artery prior to its use as a conduit for external carotid artery to internal carotid artery (EC-IC) bypass, computed tomographic angiography (CTA) has become increasingly used in the diagnostic assessment of cerebral vasculature. We demonstrate the application of CTA for evaluation of the superficial temporal artery as a vascular conduit for EC-IC bypass., Case Presentation: A female in the fourth decade of life presented with the chief complaint of headache. CTA of the Circle of Willis revealed an unruptured fusiform aneurysm of the M1 segment of the right middle cerebral artery (MCA). We performed CTA for the preoperative assessment of the STA for a putative EC-IC bypass procedure, and correlated this to conventional external carotid angiography. Reformatted CTA provided excellent surface visualization of the STA and its course in relationship to the cranial and zygomatic surfaces, and correlated well with findings on the conventional angiogram., Conclusion: CTA may eventually prove sufficient for use in assessing the STA in preparation for EC-IC bypass.

This study examined the factors influencing the proportion of underrepresented minority students (URM) in dental schools. Using a comprehensive recruitment model, it considered the relative importance of community characteristics (population demographics, oral health policies, dental care system, and university environment), dental school characteristics (Pipeline-supported, mission, and financing), and community-based dental education (CBDE) characteristics of the dental school on recruitment of URM students. Data come from a national survey of dental school seniors and a variety of publicly available sources. Three outcome variables measure URM recruitment: percent URM, percent Hispanic, and percent African American in the first year of dental school. Multivariable results revealed that the most important factors predicting a higher percent URM in first-year classes were a higher proportion of URM clinical faculty and graduating students' perceptions that their clinical rotation experience improved their ability to care for diverse groups. For percent Hispanic in the first year, a higher proportion of URM clinical faculty and students spending more time in clinical rotations predicted greater Hispanic recruitment. Graduating students' perceptions that they were less prepared to treat diverse groups were directly associated with the proportion of Hispanic students in the class. For a higher percent of African Americans in the first-year class, the most important factors were a higher proportion of blacks in the county, support from the national Pipeline program, and graduating students' perceptions of better preparedness to integrate cultural differences into treatment planning. Higher total financial aid awarded by the school was negatively associated with recruitment of African Americans. Results suggest some improved URM recruitment strategies for dental schools.

Introduction: Over-the-counter herbal and alternative medicines are classified as dietary supplements and, unlike drugs, are not rigorously regulated by the United States Food and Drug Administration. Their potential adverse effects are often poorly characterized., Method: Red clover, dong quai, and Siberian ginseng are herbal compounds used for treatment of perimenopausal symptoms such as hot flashes. These compounds are known to contain coumarins, and thus carry the potential for hemorrhagic complications; however, no cases of intracranial hemorrhage have been reported., Discussion: We report a 53-year-old woman with spontaneous subarachnoid hemorrhage due to the use of an herbal supplement containing red clover, dong quai, and Siberian ginseng.

Objective: To determine the spectrum and prevalence of the varied manifestations, associated conditions and laboratory abnormalities of patients with primary Sjögren's syndrome in Israel and compare them between individuals of Sephardic and Ashkenazi descent and with data from the literature., Methods: A retrospective study of a cohort of 201 consecutive patients diagnosed and followed at a single academic medical center. All cases were diagnosed using stringent criteria according to the American European Concensus Group including a labial minor salivary gland biopsy in all cases., Results: Patients' mean age was 57 years and 84% were women. Overall, more than 98% of patients had sicca symptoms of dry eyes and mouth. About 35% of the cohort had hematological manifestations--primarily immune cytopenias, protein immunoelectrophoresis abnormalities and lymphoma. About 20% had associated neurological conditions (not only peripheral but often central nervous system) and 15% had pulmonary involvement. In addition, thyroid disease, liver disease, vascular or cutaneous manifestations, synovitis, ocular and renal disease could be found. In fact, the presenting manifestation was extraglandular or an abnormal test result in 39% of the patients., Conclusion: No significant differences were found in glandular or extraglandular manifestations or laboratory test results between Ashkenazi and Sephardic patients, despite their genetic differences. A negative history of sicca symptoms effectively rules out primary Sjögren's syndrome in this cohort. These symptoms may not be volunteered by patients and the large variety of extraglandular involvement patterns and associated conditions observed may dominate the patient's presentation, and mandate physicians' awareness and a high index of suspicion for a timely diagnosis.

The combination of induced hypertension, hypervolemia, and hemodilution (triple-H therapy) is often utilized to prevent and treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Although this paradigm has gained widespread acceptance over the past 20 years, the efficacy of triple-H therapy and its precise role in the management of the acute phase of SAH remains uncertain. In addition, triple-H therapy may carry significant medical morbidity, including pulmonary edema, myocardial ischemia, hyponatremia, renal medullary washout, indwelling catheter-related complications, cerebral hemorrhage, and cerebral edema. This review examines the evidence underlying the implementation of triple-H therapy, and makes practical recommendations for the use of this therapy in patients with aneurysmal SAH.

As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 microm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections.

Objective: Survival of cardiac arrest (CA) after aneurysmal subarachnoid hemorrhage (SAH) is poorly characterized. We analyzed the clinical course and outcome of patients who survived resuscitation for CA after aneurysmal SAH., Methods: Medical records of all patients with acute SAH treated at Mayo Clinic between 1990 and 1997 were reviewed. Three hundred five consecutive patients with angiographically proven aneurysmal SAH presenting within 7 days of ictus were analyzed. CA was defined as a pulseless state, documented by medical personnel, for which resuscitation was performed. Outcome was measured with the Glasgow Outcome Scale score at longest follow-up (mean, 16 mo)., Results: Data from 11 patients (3.6%) who had 14 episodes of CA were analyzed. Six patients had CA before reaching the hospital and were successfully resuscitated. Nine of 14 CA episodes occurred at hemorrhage or rehemorrhage. No patient with in-hospital CA failed to be resuscitated. Overall mortality in patients who had CA (46%) was higher than that of patients without CA (15%; P = 0.019). Outcome for all patients who had CA (mean Glasgow Outcome Scale score, 2.5) was worse than for patients without CA (mean Glasgow Outcome Scale score, 3.9; P = 0.005). However, half of the survivors of CA after SAH were living independently with limited deficit at longest follow-up., Conclusion: Most cases of CA occur at the time of initial or recurrent SAH. Resuscitation for in-hospital CA is likely to be successful. Although CA after aneurysmal SAH is associated with significantly higher mortality, the outcome of survivors of CA is not worse than that for other patients after aneurysmal SAH.

This article describes the conceptual and analytical framework that will be used to assess the effectiveness of the Pipeline, Profession, and Practice: Community-Based Dental Education Program. The evaluation will use a mixed method qualitative and quantitative data collection, analysis, and triangulation. Baseline measures are reported using data from the 2003 ADEA survey of dental school seniors. Baseline measures show the dental schools are confronting a major recruitment challenge that will require short and long pipeline efforts to attract and retain underrepresented and low-income (URM/LI) persons. Gaps were found between the perceptions of URM and non-URM students in the adequacy of the curricula. The majority of all seniors described the current extramural clinical rotations as positive experiences, but URMs were more likely to report the experience improved their ability to care for diverse groups.

Object: Previous studies have indicated an increased incidence of death in patients with subarachnoid hemorrhage (SAH) who are currently receiving anticoagulation therapy. The significance of previous aspirin use in patients with SAH is unknown. The authors analyzed the effects of prior aspirin use on clinical course and outcomes following aneurysmal SAH., Methods: The medical records of 305 patients with angiogram-confirmed aneurysmal SAH who consecutively presented to our institution between 1990 and 1997 within 7 days of ictus were analyzed. Twenty-nine (9.5%) of these patients had a history of regular aspirin use before onset of the SAH. The Glasgow Outcome Scale (GOS) was used to measure patient outcome at the longest available follow up. Aspirin users were older on average than nonusers (59 years of age compared with 53 years; p = 0.018). The mean admission Hunt and Hess grades of patients with and without aspirin use were similar (2 compared with 2.3; p = 0.51). Two trends, which did not reach statistical significance, were observed. 1) The rebleeding rate in aspirin users was 14.3%, compared with a 4.7% rebleeding rate in nonusers (p = 0.06). 2) Permanent disability from vasospasm was less common among aspirin users (23% compared with 50%; p = 0.069). Outcomes did not differ between aspirin users and nonusers (mean GOS Score 3.83 compared with GOS Score 3.86, respectively; p = 0.82)., Conclusions: Despite trends indicating increased rebleeding rates and a lower incidence of permanent disability due to delayed ischemic neurological deficits, there was no significant effect of previous aspirin use on overall outcome following aneurysmal SAH. Based on these preliminary data, the presence of an intracranial aneurysm is not a strict contraindication to aspirin use.

Background and Purpose: Angioplasty and intra-arterial papaverine are promising treatments for severe symptomatic vasospasm after subarachnoid hemorrhage (SAH), but there is little information on the clinical factors that predict treatment outcome. We sought to determine variables for predicting functional outcome in this setting., Methods: We reviewed 81 consecutive patients with symptomatic cerebral vasospasm from aneurysmal SAH treated with percutaneous balloon angioplasty or selective intra-arterial papaverine infusion between 1990 and 2000 (105 procedures). Logistic regression analysis was used to assess the effect of various clinical and angiographic factors on outcome., Results: Mean patient age was 54 years (range, 29-88 years). Twenty-nine patients (36%) presented with poor-grade (World Federation of Neurologic Surgeons [WFNS] grade IV or V) SAH. Clinical deficits were global in 55 patients (70%), and angiographic vasospasm was diffuse in 53 (65%). Endovascular treatment consisted of transluminal angioplasty alone (18 procedures, 17%), intra-arterial papaverine infusion (65 procedures, 62%), or both (22 procedures, 21%). Unequivocal arterial dilatation was achieved in all but two patients, and major complications occurred in 2% of the procedures. Ten patients (12%) died in the hospital, and 36 (44%) recovered poorly. Permanent deficits attributable to cerebral vasospasm were present in 37 patients (52% of survivors). On multivariate logistic regression analysis, advanced age and poor WFNS grade at presentation were predictive of poor clinical outcome., Conclusion: Advanced age and poor clinical status at the time of SAH onset are predictive of poor clinical outcome despite endovascular treatment with angioplasty or intra-arterial papaverine in patients with symptomatic vasospasm.