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A complex skin structure (such as a nipple) can be successfully decellularized under conditions that prevent extracellular matrix crosslinking or undue matrix degradation [1]. This treatment removes cellular antigens, thus mitigating immunorejection concerns and enabling allogeneic transplantation for nipple reconstruction after mastectomy. Non-human primate studies have shown that host-mediated re-vascularization and re-epithelization of the decellularized nipples occurs within six weeks and nipple projection is maintained over the same timeframe [1]. The mechanisms by which a decellularized graft located on the surface of the body heals are incompletely understood, but are likely to follow a similar path to decellularized allografts that are implanted within the body, with some modifications. The following is a description of probable temporal events leading to healing under this circumstance.

Objective To determine the effect of instrumentation of suture material on knot security and tensile strength. Study Design In all, 5 types of suture material were used; 10 knots were tied without any instrumentation and 10 knots were tied with a hemostat holding tension on the first throw while the second throw was made for each suture type. Each group was tested to failure with the maximum load and mode of failure recorded. The maximum load between groups of each suture type was compared; frequency of failure through knot slippage vs material fracture was also compared between groups. Results There was no significant difference observed in the maximum load to failure for any suture type between instrumented and noninstrumented groups. Additionally, there was no difference between any instrumented and noninstrumented groups for material failure vs failure due to knot slippage. Conclusions Instrumentation of suture material during two-hand tying does not affect the strength of suture material or knot security.

The effects of blast exposure have gained increasing interest in the military medical community with their continued occurrence on the battlefield. The impact of the direct and indirect energy imparted from blasts to hollow viscera, as well as closed head injuries, have been well studied. However, the injury to articular cartilage has not been investigated, despite previous correlations regarding the development of osteoarthritis. The purpose of this study was to assess the degree of injury to articular chondrocytes after exposure to a simulated blast overpressure wave.Fresh juvenile porcine stifle joints were subjected to a simulated blast overpressure wave utilizing a custom fabricated blast simulator with compressed gases, within the reported range of observed battlefield blasts. Chondrocyte viability was assessed with live/dead staining using ethidium homodimer-2 and calcien acetoxymethylester stain and confocal laser scanning microscopy, calculated as a ratio of dead chondrocytes to live chondrocytes. Testing was performed at time points of 2, 4, and 8 hours after blast exposure and was compared with unblasted control samples.Chondrocyte viability decreased after exposure to a blast overpressure wave when compared with control samples. The amount of death was greater closer to the articular surface and dissipated with increasing tissue depth. Chondrocyte death increased with time after exposure.Chondrocyte death is present after exposure to a simulated blast wave. There is an inverse relationship between chondrocyte viability and the depth from the articular surface. Additional studies are needed to further characterize dose and time effects of blast exposure.

The chondrotoxicity of local anesthetics has been previously recognized. Recent introduction of a liposomal formulation of bupivacaine has been found to significantly improve postoperative pain control but its effect on chondrocyte viability has yet to be investigated with this new formulation. We sought to assess the in vitro chondrotoxicity of liposomal bupivacaine.Chondrocytes were isolated from articular cartilage from fresh stifle joints and grown in culture medium. Cultured chondrocyte-derived cells (CDCs) were treated with 0.9% normal saline solution, 0.5%, 0.25%, and 0.13% bupivacaine and ropivacaine, 1.3% liposomal bupivacaine for 1 hour. Following treatment, cells were washed and incubated in media for 23 hours. The CDCs were then harvested and viability was assessed by flow cytometry using SYTOX green dead cell stain.Treated CDCs demonstrated a dose-response effect for chondrocyte viability when treated with bupivacaine, ropivacaine, and liposomal bupivacaine. Liposomal bupivacaine demonstrated the highest chondrocyte viability following treatment. Ropivacaine demonstrated higher chondrocyte viability than bupivacaine.Following 1 hour of treatment, liposomal bupivacaine demonstrated the highest chondrocyte viability. Chondrocyte viability was inversely proportional to anesthetic concentration.

The Industry Committee of the Tissue Engineering Regenerative Medicine International Society, Americas Chapter (TERMIS-AM) administered a survey to its membership in 2013 to assess the awareness of science requirements in the U.S. Food and Drug Administration (FDA) regulatory process. One hundred forty-four members responded to the survey. Their occupational and geographical representation was representative of the TERMIS-AM membership as a whole. The survey elicited basic demographic information, the degree to which members were involved in tissue engineering technology development, and their plans for future involvement in such development. The survey then assessed the awareness of general FDA scientific practices as well as specific science requirements for regulatory submissions to the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), and the Office of Combination Projects (OCP). The FDA-specific questions in the survey were culled from guidance documents posted on the FDA web site ( www.fda.gov ). One of the answer options was an opt-out clause that enabled survey respondents to claim a lack of sufficient awareness of the topic to answer the question. This enabled the stratification of respondents on the basis of confidence in the topic. Results indicate that across all occupational groups (academic, business, and government) that are represented in the TERMIS-AM membership, the awareness of FDA science requirements varies markedly. Those who performed best were for-profit company employees, consultants, and government employees; while students, professors, and respondents from outside the USA performed least well. Confidence in question topics was associated with increased correctness in responses across all groups, though the association between confidence and the ability to answer correctly was poorest among students and professors. Though 80% of respondents claimed involvement in the development of a tissue engineering technology, their responses were no more correct than those who were not. Among those developing tissue engineering technologies, few are taking advantage of existing standards organizations to strengthen their regulatory submissions. The data suggest that early exposure to regulatory experts would be of value for those seeking to bring their technology to the market. For all groups studied but especially for students and professors, formal initial or continuing education in Regulatory Science should be considered to best support translational tissue engineering research and development. In addition, the involvement of standards development organizations during tissue engineering technology development is strongly recommended.

Objectives To evaluate the antimicrobial activity of a new, transparent composite film dressing, whose adhesive contains chlorhexidine gluconate (CHG), against the native microflora present on human skin. Methods CHG-containing adhesive film dressings and non-antimicrobial control film dressings were applied to the skin on the backs of healthy human volunteers without antiseptic preparation. Dressings were removed 1, 4 or 7 days after application. The bacterial populations underneath were measured by quantitative cultures (cylinder-scrub technique) and compared with one another as a function of time. Results The mean baseline microflora recovery was 3.24 log10 cfu/cm(2). The mean log reductions from baseline measured from underneath the CHG-containing dressings were 0.87, 0.78 and 1.30 log10 cfu/cm(2) on days 1, 4 and 7, respectively, compared with log reductions of 0.67, -0.87 and -1.29 log10 cfu/cm(2) from underneath the control film dressings. There was no significant difference between the log reductions of the two treatments on day 1, but on days 4 and 7 the log reduction associated with the CHG adhesive was significantly higher than that associated with the control adhesive. Conclusions The adhesive containing CHG was associated with a sustained antimicrobial effect that was not present in the control. Incorporating the antimicrobial into the adhesive layer confers upon it bactericidal properties in marked contrast to the non-antimicrobial adhesive, which contributed to bacterial proliferation when the wear time was ≥4 days.

Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process, in turn, depends on observational data gathered from patients, communities, and public health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation's academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding.To address these serious and systemic problems, in 2006 the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program's overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation's academic health centers.

Contains fulltext : 53200.pdf (Publisher’s version ) (Open Access) The field of tissue engineering is developing rapidly. Given its ultimate importance to clinical care, the time is appropriate to assess the field's strategic directions to optimize research and development activities. To characterize strategic directions in tissue engineering, a distant but reachable clinical goal was proposed and a worldwide body of 24 leaders in tissue engineering was queried systematically to determine the best paths toward that goal. Using a modified Hoshin process, we identified 14 critical activity categories and then stratified them by their immediate priority for the field. The result of the analysis illustrates a highly interdependent set of activities that are dominated by the need for an understanding of angiogenesis, stem cell science, and the utilization of molecular biology and systems biology tools to enable a deeper comprehension of tissue development and control.

Conventional coronary angiography is currently the gold standard in the detection and diagnosis of coronary artery disease. This modality, however, is invasive in nature. Hence, there is a need for noninvasive imaging techniques to provide comprehensive assessment of coronary artery disease, especially in stable patients at low to moderate risk of disease. In recent years, a number of noninvasive modalities have found wide applications in cardiac imaging. Most recent investigations have used magnetic resonance imaging, multislice computed tomography and electron-beam computed tomography scanners. This review discusses the clinical challenges existing in the field of cardiac imaging and focuses on the technical advancements of multislice computed tomography scanners that have made them a very attractive noninvasive option for the detection and diagnosis of coronary artery disease.

To show all cardiac evaluations multislice computed tomography (MSCT) can perform. Methods: MSCTs were performed on an MSCT scanner (Mx8000; Philips Medical Systems) with enhanced contrast acquisition. The reconstructed images were sent to a workstation for multiplanar reconstruction, volume rendering, and 3-D reconstruction. A total of 140 patients were studied with MSCT and conventional angiography (CA) to assess coronary artery stenosis. 30 of these patients were also evaluated by intravascular ultrasound (IVUS) for plaque characterization. A group of 20 patients were studied with MSCT, gated single-photon emission computed tomography (SPECT), and echocardiography for myocardial perfusion test and volumetric analysis. Results: The results of MSCT versus CA showed a sensitivity of 79.2% and a specificity of 93.7%, whereas for MSCT versus IVUS the sensitivity was 84.4% and the specificity 91.6%. A total of 156 plaques were detected by both methods. 105 (67%) were soft, 14 (24%) were fibrous and 37 (9%) were calcified. In the evaluation of myocardial perfusion, the cardiac software showed a sensitivity of 55% and a specificity of 80%. However, general evaluation disclosed a sensitivity of 88.5% and a specificity of 96.4%. The volumetric analysis showed a good correlation between MSCT and echocardiography for end-systolic volume (ESV), rS = 0.874, and end-diastolic volume (EDV), rS = 0.828. There was also a good correlation for the evaluation of the left ventricular anatomy: septal wall rS = 0.96, posterior wall rS = 0.81, and diameter of left ventricle rS = 0.69. Conclusion: Nowadays, MSCT allows different cardiologic evaluations with the same acquisition as that for the coronary arteries. These data show a general view of the patient providing information that is obtained by the hand of multiple cardiologic methods such as DA, IVUS, gated SPECT, and echocardiography.

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Although the relationship between regional facial muscle activity and resultant displacement of the face is important to the refinement of many of the treatments of facial paralysis and palsy, this relationship has not been adequately explored. We analyzed the relationship between frontalis muscle activity as measured with surface electromyography and the associated eyebrow displacement as measured with the maximal static response assay in 16 human volunteers. We hypothesized that graded, sustained muscle activity would correlate with graded, sustained elevation of the eyebrow. We found that (1) the relationship between the muscle activity and the corresponding displacements was best described by activity versus displacement squared (r2 = 0.993); (2) there was a wide variation between individual brows for the relationship between muscle activity and displacement; (3) there was a normal amount of asymmetry of the relationship between muscle activity and displacement between the two brows of a subject; (4) left and right frontalis generated the same amount of muscle activity, but left brows elevated significantly higher; (5) the method of simultaneous measurement of muscle activity and displacement used in this study yielded results similar to those previously reported; and (6) the methods used in this study are useful to further investigate the relationship between muscle activity and displacement. (Plast. Reconstr. Surg. 104: 1789, 1999.)

Only recently have scientists come to appreciate that many tissues and cell populations that were formerly considered to be in a terminally differentiated state are capable of division and or dedifferentiation. It is the goal of the tissue engineer to understand and redirect this potential. Muscle tissue-engineering efforts will be directed toward building in vitro replacements for in vivo problems. Tissue-engineering advances will be interdependent with advances in gene therapy techniques to restore function at a cellular level.

Generating skeletal muscle in vitro is an attractive approach to overcome problems associated with autologous transfer of muscle and donor site morbidity during plastic surgery. Such tissue engineering requires application of biomaterials that selectively control the attachment, morphology, and proliferation of muscle progenitor ("satellite") cells. This study examined the initial attachment, morphological characteristics, and proliferative behavior of murine C2C12 myoblasts on glass substrata derivatized with self-assembled monolayers (SAMs) of the organosiloxanes N-(2-aminoethyl)(3-aminopropyl)trimethoxysilane (EDA) and tridecafluoro-1,1,2,2-tetrahydrooctyl-1-dimethylchlorosil ane (13F). The fraction of myoblasts resisting detachment upon rinsing was greater on EDA than on 13F. Application of a quantitative moments-based analysis of cell morphology demonstrated that projected area and two size-invariant metrics of shape (extension and dispersion) for these cells were greater for EDA than for 13F. Myoblasts also proliferated faster on EDA than on 13F. These data indicate that EDA-derivatized glass provides a superior substratum for myoblast culture compared to 13F-derivatized glass. Understanding myoblast behavior on these biomaterials that promotes contrasting cellular responses is the first step toward using patterned SAMs to control myotube alignment for tissue engineering skeletal muscle.

For cardiovascular biomaterials, thrombosis, thromboembolism and vascular graft occlusion are believed to be precipitated by the adsorption of proteins containing adhesive ligands for platelets. Polyethylene-glycol-diisocyanate(PEG-diisocyanate, 3400 MW) may potentially react with protein amines to form molecular barriers on adsorbed proteins on biomaterials, thereby masking adhesive ligands and preventing acute surface thrombosis. To test this notion, PE, PTFE, and glass microconduits were pre-adsorbed with fibrinogen and treated with PEG-diisocyanate, non-reactive PEG-dihydroxyl, or remained untreated. Following perfusion of 111In-labeled platelets in whole human blood for 1 min (wall shear rate = 312 s(-1)), PEG-diisocyanate treated surfaces experienced 96%(PE), 97%(PTFE) and 94% (glass) less platelet deposition than untreated surfaces. Similar reductions were seen for PEG-diisocyanate versus PEG-dihydroxyl treatment. Low shear perfusions of plasma for one hour prior to blood contact did not reduce the inhibitory effect of PEG-diisocyanate. Platelet adhesion onto collagen coated glass coverslips and platelet deposition onto preclotted Dacron was also reduced by treatment with PEG-diisocyanate (93 and 91%, respectively). Protein-reactive PEG may thus have utility in forming molecular barriers on surface associated proteins to inhibit acute thrombosis on cardiovascular biomaterials.

The purpose of this study was to determine if stable facial paresis of the frontalis muscle represents a model for autologous myoblast therapy. It was hypothesized that stable facial paresis of the frontalis muscle can be quantitatively differentiated from the motion of normal and completely paralyzed frontalis muscles, respectively. The Maximal Static Response Assay of Facial Nerve Function was used to quantitate maximal excursion of the skin overlying the frontalis muscle, as indicated by eyebrow raise, in a group of normal individuals and a group of patients with clinically defined complete hemifacial paralysis. For patients in each group, a ratio of weak sided brow motion to strong sided brow motion (brow motion ratio) was calculated. Brow motion ratios of normal individuals were significantly different than those of patients with complete hemifacial paralysis. Importantly, a wide range of brow motion ratios exists between these two groups. This range was defined to quantitatively represent hemifacial...

The aesthetics of a smile have been shown to be related to the symmetry of the smile, the curvature of the upper lip, and the arc of curvature of the lower lip to the incisal edges of the upper teeth. The present study quantitatively compares the magnitude of facial animation (as determined by the Johnson Maximal Static Response Assay) to the aesthetics of a smile in 25 subjects. The assay (software) calculates two-dimensional facial movement changes from the frontal view, as measured by the relative change in position of seven facial landmarks. Smile shape and lip fullness were also categorized. Lip fullness was the only variable found to correlate with the aesthetics of a smile. The magnitude of facial movement, smile shape, and gender did not correlate with aesthetic ratings.

Integration of impairment measures and disability measures may provide clinicians with an accurate and comprehensive picture of the patient’s dysfunction. The purpose of this study was to indicate the usefulness of two new scales of measuring facial impairment and disability in describing characteristics of individuals with facial neuromuscular dysfunction. Fifty-one individuals with unilateral facial neuromuscular dysfunction and a House-Brackmann grade of III or higher were included in the study. The subjects’ movement impairments were assessed using the Facial Grading System (FGS). The subjects reported their physical and social function on the Facial Disability Index (FDI). Nine variables were subjected to a confirmatory principal-components factor analysis to indicate important factors in describing patients with facial nerve disorders. The confirmatory principal-components factor analysis identified three factors, impairment, disability, and temporal characteristics of disease, accounting for 72% of the variance in describing individuals with facial neuromuscular dysfunction. Integration of these measures may provide clinicians with an accurate and comprehensive picture of the patient’s dysfunction, thus aiding in the determination of intervention and the measurement of clinical outcomes. (Otolaryngol Head Neck Surg 1997;117:315-21.)

OBJECTIVE: The prognostic significance of quantitative measurement of tumor proliferative activity was evaluated for oligodendroglial tumors. METHODS: Ki-67/MIB-1 immunochemistry was used to measure proliferative activity in 81 oligodendrogliomas and oligoastrocytomas. The relationships among survival, proliferation, histological features, and clinical variables were evaluated using a Cox proportional hazards analysis. RESULTS: After stratifying by histological grade and adjusting for age at diagnosis, there was a significant association between the Ki-67/MIB-1 labeling index (LI) (percentage of positive cells) and survival (P = 0.04). This association was illustrated further by the significantly different survival of two groups based on LI ranges of less than or equal to 5 and greater than 5 (P < 0.0001). CONCLUSION: The poor correlation between mitotic figures and survival in oligodendrogliomas that has been reported previously emphasizes the need for an accurate method to measure proliferative activity. Our study demonstrated the usefulness of the Ki-67/MIB-1 LI and demonstrated that LI ranges can be defined for clinical application.

The purpose of this paper is to describe the outcome of facial neuromuscular retraining for brow to oral and ocular to oral synkinesis in individuals with facial nerve disorders. Fourteen patients with unilateral facial nerve disorders and oral synkinesis who were enrolled in physical therapy for retraining were studied. Synkinesis was measured with quantitative video facial position analysis prior to the initiation of physical therapy and at regular intervals during retraining. Retraining included surface electromyographic biofeedback-assisted specific strategies for facial muscle reeducation and a home exercise program of specific facial movements. Twelve of 13 patients with brow to oral synkinesis and 12 of 14 patients with ocular to oral synkinesis reduced their synkinesis with retraining. Patients with a 1-year on greater duration of a facial neuromuscular disorder (excluding patients with unusually marked changes) demonstrated a significant decrease in brow to oral synkinesis and in ocular to oral synkinesis; there was a mean percentage decline in abnormal movement of 60.5 percent (SD = 26.48) and 30.1 percent (SD = 62.57), respectively. We conclude that brow to oral and ocular to oral synkineses associated with partial recovery from facial paralysis were reduced with facial neuromuscular retraining for individuals with facial nerve disorders.

BACKGROUND Accurate histologic diagnosis of gliomas is fundamental to proper patient management and to the interpretation of basic and clinical investigations. Diagnostic accuracy and reproducibility are compromised by the subjective histologic criteria currently used to classify and grade gliomas. METHODS The histologic features of 4 sets of gliomas (a total of 244 cases) were reviewed independently by 4 neuropathologists to determine interobserver diagnostic concordance rates. Cases wherein diagnostic disagreements arose were reviewed jointly to identify and refine the histologic criteria that were adversely affecting diagnostic reproducibility. Using the criteria developed in the study, a set of 315 gliomas with known survival data was evaluated in order to validate the usefulness of the criteria. RESULTS There was significant improvement in diagnostic concordance with each session (P = 0.02). For the first session, the concordance rates were as follows: all 4 reviewers, 52%; any 3 reviewers, 60%; 2 reviewers, 70%. For the fourth session, the respective rates were 69%, 75%, and 80%. Although features important in grading, particularly microvascular proliferation, were sometimes problematic, most disagreements related to the classification of tumors. Much of the improvement related to the refinement of criteria distinguishing diffuse astrocytomas from oligodendrogliomas/oligoastrocytomas and pilocytic astrocytomas. It was concluded that the presence of any typical oligodendroglioma was sufficient to remove a tumor from the astrocytoma category. CONCLUSIONS The authors' data indicate that oligodendroglial tumors comprise up to 25% of gliomas, a significantly higher proportion than was previously recognized. The data also suggest that the wide range of survival times reported for patients with anaplastic astrocytoma may reflect "contamination" resulting from misdiagnosis, particularly of oligodendroglial tumors and pilocytic astrocytomas. Cancer 1997; 79:1381-93. © 1997 American Cancer Society.

SummaryAn alternative method of uniting small diameter vessels to obtain tissue union while limiting the thrombogenic effect of suture placement at a vessel anastomosis involves the use of a thrombin based fibrin glue as a surgical sealant. This investigation addresses whether the in vitro application of a thrombin based glue (TG), or batroxobin glue (BG), a non-thrombin based glue made with the snake venom enzyme batroxobin, alters intravascular platelet deposition (PD) or cleaves blood fibrinogen, as measured by fibrinopeptide A (FPA) production, when the respective glue is applied to the external surface of an intact human placental artery or an artery with an anastomosis.When TG was applied to the adventitial surface of an intact vessel or an anastomosis (n = 7) of control and experimental vessels, there was a significant increase in intraluminal platelet deposition, an effect not realized with BG (n = 12, intact vessel TG p = 0.01, BG p = 0.66, anastomosis TG p The data suggest that TG and BG are drug delivery systems for their respective enzymes that either pass through or transfer a message across not only a surgically created anastomosis, but also an intact vessel wall.

We studied myelin proteins and glycolipids in 24 human oligodendrogliomas (16 pure, eight mixed), including two grade I, 13 grade II, five grade III, and four grade IV. Tumours with a 1b ganglioside content (GD1b, GT1b and GQ1b) over 30% of total gangliosides occur more frequently in the WHO grade I and II (47%) and grade III (40%) than in the grade IV (25%) group; there was no difference in the amounts of total ganglioside or individual gangliosides between pure and mixed oligodendrogliomas. The presence of 6'-LM1 correlated with higher grades of tumours (chi 2 P approximately 0.02); however, 3'-LM1 and total neolacto-series gangliosides did not correlated with grade. Immunohistochemical studies of oligodendrocyte and myelin markers (GalCer, sulfatide, 2',3' -cyclic nucleotide phosphodiesterase, myelin basic protein and proteolipid protein) using specific antibodies showed only a very small proportion of tumour cells staining. These data do not support the hypothesis that tumours classified as oligodendrogliomas are derived from mature oligodendrocytes.

The human microvascular anastomosis represents a localized environment with strongly thrombotic tendencies. In previous studies, an increase in initial platelet deposition at a human ex vivo anastomosis was measured. It is postulated that this increase in anastomotic platelet deposition was due to a reduction in anastomotic prostacyclin production as a consequence of local endothelial cell injury or loss. Instead, in this study, an increase in anastomotic prostacyclin production over unsutured controls (control 1093 +/- 222 pg/ml of 6-keto prostaglandin F (PGF) 1-alpha, n=21; anastomosis 2494 +/- 414, n=21, mean +/- 1 SEM, p=0.005) is demonstrated. Anastomotic prostacyclin production was augmented by addition of arachidonic acid (0.1 mM) (39,000 +/- 11,300 pg/ml of 6-keto PGF 1-alpha, n=7, p0.001) and suppressed by the preincubation of vessel segments with aspirin in a dose-dependent fashion (1mM) (83+/-22 pg/ml of 6-keto PGF 1-alpha, n=21, p0.001); aspirin (0.1 mM) (312 +/- 56 pg/ml of 6-keto PGF 1-alpha, n=7, p0.001). In further studies using a perfusion apparatus of human blood pumped through human placental artery segments, suppression of prostacyclin production did not augment initial platelet deposition (control anastomosis 4.9 +/- 2.2 x10(6) platelets per cm2, aspirin treatment 6.0 +/- 2.8 x 10(6) platelets per cm2, n=5, mean +/- 1 SEM, p0.05). Suppression of platelet function with aspirin (0.1 mM) also did not decrease initial platelet deposition onto the anastomosis (5.8 +/- 2.8 x 10(6) platelets per cm2, n=r, p0.05). In this model system, initial platelet deposition at the anastomosis may not be dependent upon cyclooxygenase pathways.

There is now a growing awareness of the central role of platelet function in microvascular thrombosis. Platelet aggregation studies remain one of the most useful ways of studying platelet function and response to different stimuli. This brief communication highlights some of the main variables that can affect platelet aggregation in rats and emphasizes the existence of important differences in these variables compared with human platelet aggregation.

The surgically created vascular anastomosis is a thrombogenic zone of uncertain etiology. This study was designed to investigate the importance of tissue factor as a cause of human microvascular thrombogenicity. The ability of tissue factor pathway inhibitor (TFPI) to block the effect of tissue factor was also tested in this whole-vessel model system. Tissue factor activity in the presence of absence of TFPI was assayed on the luminal surface of dissected human placental arteries, on the advential surface, and also at the site of a microvascular anastomosis. Vessel wall thrombin activity was measured in the presence and absence of TFPI. Platelet deposition onto a vessel surface using a perfusion system was measured with and without TFPI. Tissue factor activity was greater on the adventitia (4.6 +/- 2.8 x 10(-4) units factor Xa generated/min) than on the endothelium (1.8 +/- 1.6 x 10(-4), P < 0.03) or at a surgically created anastomosis (2.1 +/- 1.2 x 10(-4), P < 0.04). TFPI reduced Xa generation to undetectable levels in 21 of 23 endothelial, adventitial, and anastomotic segments (P < 0.002). TFPI significantly reduced vessel wall thrombin activity in comparison to control anastomoses (control, 3.2 +/- 1.7 ng fibrinopeptide A (FPA)/(ml x min); TFPI, 1.4 +/- 1.2 ng FPA/(ml x min); P < 0.0001). TFPI reduced the platelet deposition on vessel segments with intact endothelium (no TFPI, 0.88 +/- 0.69 x 10(6) platelets/cm2; TFPI, 0.49 +/- 0.29 x 10(6) platelets/cm2; P < 0.06) and on vessel segments with anastomoses (no TFPI, 1.3 +/- 0.70 x 10(6) platelets/cm2; TFPI, 0.76 +/- 0.35 x 10(6) platelets/cm2; P < 0.02). This study demonstrates the importance of tissue factor as a thrombogenic element in a human whole-vessel model system. TFPI is effective in reducing this thrombogenicity.

WE REPORT A previously undescribed hamartoma of the Vlllth nerve, consisting of adipose tissue, Schwann cells associated with myelinated nerve fibers, well-differentiated smooth and striated muscle fibers, and rare ganglion cells. The tumor was found in 35-year-old Caucasian female who presented with right-sided hearing loss. The mass, which we designate an ectomesenchymal hamartoma, most likely developed from pluripotent neural crest cells (ectomesenchyme), which are capable of differentiating into a variety of neuroectodermal and mesenchymal cell types. The development of the neural crest, the concept of ectomesenchyme, and the histogenesis of this tumor are reviewed. (Neurosurgery 37 :1 204-1207, 1 995)

BACKGROUND Classification/grading schemes for brain tumors are based mainly on histologic examinations, but these have major limitations, which has led to a search for more objective prognostic markers. Gangliosides have several biologic effects relevant to tumors, and ganglioside compositions of primary brain tumors correlate with diagnosis. This led to the authors' hypothesis that ganglioside patterns of brain tumors might be useful as prognostic indicators. METHODS Gangliosides in primary brain tumors of different histologic types from 84 patients were analyzed. Specific ganglioside patterns and several other relevant variables were examined for associations with survival using a Cox proportional hazards model. Kaplan-Meier survival curves were analyzed using the log-rank test. RESULTS Patients in whom less than 30% of total tumor gangliosides consisted of 1b pathway gangliosides (GD1b, GT1b, and GQ1b) had significantly higher risk ratios than those with more than 30% 1b gangliosides (P approximately 0.03). The presence of 6'-LM1 (NeuAc alpha 2-->6Gal beta 1-->4Glc-NAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer was also associated with a higher risk ratio (P approximately 0.007). Combinations of 1b gangliosides and 6'-LM1 identified three groups of patients regardless of histologic diagnosis. Group A, with less than 30% 1b and the presence of 6'-LM1, had a median survival time of 331 days. Group B, with less than 30% 1b but no 6'-LM1, had a median survival time of more than 698 days. Group C, with more than 30% 1b had a median survival time of more than 776 days. CONCLUSIONS The correlation of ganglioside patterns with survival in this initial investigation suggests the potential of 1b gangliosides and 6'-LM1 to be used as prognostic indicators. Continuing research is being conducted to assess this possibility prospectively.

Article abstract-Objective: Clinicopathologic evaluation of patients with lower extremity paraparesis/-plegia following rupture and repair of anterior communicating artery (ACoA) aneurysms. Design: Institution-based retrospective review. Setting: A tertiary neurologic referral center. Patients, participants: Seven of 101 patients with subarachnoid hemorrhage from ruptured ACoA aneurysms treated between January 1987 and December 1992. Main outcome measures: Neurologic status at latest follow-up examination. Results: All patients presented with severe hemorrhage, poor clinical grade, and intracranial hypertension. Motor deficits developed within 7 days of aneurysm rupture and persisted for a mean duration of 39 days. Angiographic evidence of vasospasm in the anterior cerebral artery (ACA) distribution was documented in all cases, and paraparesis persisted beyond the angiographic resolution of vasospasm. All patients had evidence of frontal lobe dysfunction throughout their postoperative courses, and deep venous thrombosis and pulmonary emboli were common causes of morbidity and mortality. Autopsy data supported regional microvascular ischemia within the ACA distribution as the etiology of these motor deficits. Conclusions: The combination of vasospasm in the ACA distribution and lower extremity weakness associated with cognitive and affective impairment that resolves with time is common in patients with ACoA aneurysms. We propose that this constellation of clinical, radiographic, and pathologic findings be referred to as the "ACoA aneurysm paraparesis syndrome".NEUROLOGY 1995;45: 45-50

The characteristics of an atmospheric pressure, RF discharge in air were determined and compared with a 2D numerical model adapted from that used for a dc glow discharge. For a 15 mm discharge, the RF plasma's electrical and optical characteristics show a close correlation to several equivalent dc plasmas and to the results calculated from the adapted model. For an rms conduction current range of 11–30 mA, the rotational temperature varies between 2800 and 3200 K; the vibrational temperature shows a change of 3500–4000 K with near equilibrium conditions to the rotational state occuring in the central region of the discharge. Spatial measurements and modelling of nitrogen emission spectra identify the changes in the temperatures and dimensions along the vertical z-axis as well as the spatial dependence on the atomic and molecular species generated in the discharge.

The Tissue Engineering and Regenerative Medicine International Society of the Americas (TERMIS-AM) Industry Committee conducted a semiquantitative opinion survey in 2010 to delineate potential hurdles to commercialization perceived by the TERMIS constituency groups that participate in the stream of technology commercialization (academia, start-up companies, development-stage companies, and established companies). A significant hurdle identified consistently by each group was access to capital for advancing potential technologies into development pathways leading to commercialization. A follow-on survey was developed by the TERMIS-AM Industry Committee to evaluate the financial industry's perspectives on investing in regenerative medical technologies. The survey, composed of 15 questions, was developed and provided to 37 investment organizations in one of three sectors (governmental, private, and public investors). The survey was anonymous and confidential with sector designation the only identifying feature of each respondent's organization. Approximately 80% of the survey was composed of respondents from the public (n=14) and private (n=15) sectors. Each respondent represents one investment organization with the potential of multiple participants participating to form the organization's response. The remaining organizations represented governmental agencies (n=8). Results from this survey indicate that a high percentage (60%) of respondents (governmental, private, and public) were willing to invest$2MM into regenerative medical companies at the different stages of a company's life cycle. Investors recognized major hurdles to this emerging industry, including regulatory pathway, clinical translation, and reimbursement of these new products. Investments in regenerative technologies have been cyclical over the past 10-15 years, but investors recognized a 1-5-year investment period before the exit via Merger and Acquisition (MA). Investors considered musculoskeletal products and their top technology choice with companies in the clinical stage of development being the most preferred investment targets. All sectors indicated a limited interest in early-stage start-up companies potentially explaining why start-up companies have struggled to access to capital and investors based their investment on the stage of a company's life cycle, reflecting each sector's risk tolerance, exit strategy, time of holding an investment, and investment strategy priorities. Investors highlighted the limited number of regenerative medical companies that have achieved commercial status as a basis for why public investors have been approached by so few companies. Based on respondents to this survey, regenerative medical sponsors seeking capital from the financial industry must keep the explanation of their technology simple, since all sectors considered regenerative medical technology as difficult to evaluate. This survey's results indicate that under the current financial environment, many regenerative medical companies must consider codevelopment or even MA as nondilutive means of raising capital. The overall summary for this survey highlights the highly varied goals and motivations for the various sectors of the government and financial industries.

Background. Limitations of classification schemes for brain tumors based solely on morphology have stimulated searches for molecular markers of nosologic and prognostic value. Gangliosides are logical candidates because there are high concentrations of them in the nervous system, there is evidence of their roles in regulation of growth and differentiation, and data from small series suggest correlations between ganglioside composition and glioma type. Methods. Ganglioside compositions were determined for 70 primary human brain tumors: 16 low grade astrocytomas (LG), 12 anaplastic astrocytomas (AA), 34 glioblastoma multiformes (GEM), and 8 primitive neuroectodermal tumors (PNET). This method involved identification and quantitation of specific gangliosides using chemical analysis and immunoanalysis. Results. Among all tumor types, histologic grade correlated with a progressive loss of 1b gangliosides (P < 0.0001). GQlb was higher in LGs than in AAs (P < 0.001). Both GTlb and GDlb were higher in AAs than GBMs (P < 0.01 and 0.05, respectively) and lower in PNETs than in GBMs (P < 0.05). GM3 was higher in PNETs than in any astrocytoma group and higher in GBMs than in either AAs or LGs. There was a significant difference in the content of 3'-LM1 among all groups (P < 0.005), between

The Kaonde inhabit the savanna woodland plateaus of the Northwestern Province of Zambia. Primarily subsistence farmers, they have developed an agricultural system that consists of a chitemene form of long fallow cultivation and various forms of continuous cultivation. The different cultivation systems involve the exploitation of different environmental locations, where they are characterised by different agricultural practices and crop assemblages. Spatial variations in agricultural land use reflect locally varying environmental conditions. Given the prevalence of the tsetse fly, the Kaonde do not raise livestock, but over the last two decades some Kaonde farmers have engaged in fish-farming as a dietary supplement and cash crop. The Northwestern Province is the least populated, least developed, and most rural province in Zambia, yet recent population growth, notably in the close-settled zone around Solwezi Township (the provincial capital), has led to changes in the Kaonde agriculture system. Population pressure has led to the shortening of the fallows associated with long fallow cultivation, and an increased emphasis on existing forms of continuous cultivation. In a modified fashion, changes in Kaonde agricultural practices support the main contention of the Boserup theory that increases in population lead to the intensification of agriculture.

Free-living amebae etiologically associated with central nervous system (CNS) infection in children have included Acanthamoeba, Naegleria, and recently, leptomyxid ameba. Two previously healthy children are reported with CNS infection caused by leptomyxid ameba, recently classified as Balamuthia mandrillaris. One child, a 27-month-old boy, had right hemiparesis and aphasia, and the other, a 13-year-old girl, had headache, right hemiparesis, diplopia, and left facial weakness. Cerebrospinal fluid studies of both children revealed a mononuclear pleocytosis and mildly elevated protein. The younger child developed seizures and progressive cerebrovascular occlusions; both developed hydrocephalus and coma progressing to death 16 days after onset of symptoms. The younger child at autopsy had necrotizing meningoencephalitis, left internal carotid arteritis, and amebic trophozoites and cysts in brain. Perivascular trophozoites were difficult to distinguish morphologically from macrophages in the older child, who had no cyst forms. Indirect immunofluorescence test revealed CNS infection with B. mandrillaris in both. This leptomyxid ameba, formerly considered an innocuous soil organism, should be considered in the differential diagnosis of progressive or atypical childhood stroke.