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Eight year outcome after surgery for lumbar disc herniation: a comparison of reoperated and not reoperated patients.

Department of Neurosurgery, University Hospital in Trondheim, Norway.
Acta Neurochirurgica (Impact Factor: 1.79). 01/2001; 143(6):607-610; discussion 610-11. DOI: 10.1007/s007010170066
Source: PubMed

ABSTRACT A retrospective study of 211 patients with unilateral sciatica operated on for lumbar disc herniation during 1988 and 1989 was performed in order to compare the results of reoperated patients with the results of patients operated on only once. The patients completed a standardized questionnaire in 1997 which included questions about reoperations, back and leg pain, functional status and disability pension. Outcome scores were calculated, giving values from 0 (no pain/normal function) to 100 (totally disabled). A follow-up status of 80.1% was obtained; 163 patients answered the questionnaire while six patients had died. 23.9% of the patients (n = 39) had been reoperated on. A recurrent disc herniation at the same level was suspected before the reoperation in 18.4%, but a recurrence was found in only 8.6%. 3.7% were reoperated on more than once. Outcome score was worse among "reoperated" patients (median 45.0, range 0-94) than among patients who only had the primary operation (median 10.5, range 0-81) (P < 0.001). In addition, 34.3% of the "reoperated" patients received a disability pension compared to 9.9% of the patients not reoperated on (P < 0.01). Patients reoperated upon at the same level without peroperative signs of recurrent disc herniation, had an outcome score of 53.0 (range 0-82) compared to a score of 30.0 (range 0-66) in patients with a confirmed recurrence (P < 0.05). The percentage of disability pension was 53.8% versus 9.1%, respectively, for those two groups (P < 0.05). Eight years after operation for lumbar disc herniation, the outcome was significantly worse in "reoperated" patients than in patients operated on once. In addition, reoperated patients with peroperatively confirmed recurrence of the same disc, seemed to have a better outcome than patients without peroperative signs of a recurrence.

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    ABSTRACT: The effectiveness of lumbar fusion for chronic low back pain after surgery for disc herniation has not been evaluated in a randomized controlled trial. The aim of the present study was to compare the effectiveness of lumbar fusion with posterior transpedicular screws and cognitive intervention and exercises. Sixty patients aged 25-60 years with low back pain lasting longer than 1 year after previous surgery for disc herniation were randomly allocated to the two treatment groups. Experienced back surgeons performed transpedicular fusion. Cognitive intervention consisted of a lecture intended to give the patient an understanding that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it. This was reinforced by three daily physical exercise sessions for 3 weeks. The primary outcome measure was the Oswestry Disability Index (ODI). Outcome data were analyzed on an intention-to-treat basis. Ninety-seven percent of the patients, including seven of eight patients who had either not attended treatment (n=5) or changed groups (n=2), completed 1-year follow-up. ODI was significantly improved from 47 to 38 after fusion and from 45 to 32 after cognitive intervention and exercises. The mean difference between treatments after adjustment for gender was -7.3 (95% CI -17.3 to 2.7, p=0.15). The success rate was 50% in the fusion group and 48% in the cognitive intervention/exercise group. For patients with chronic low back pain after previous surgery for disc herniation, lumbar fusion failed to show any benefit over cognitive intervention and exercises.
    Pain 06/2006; 122(1-2):145-55. DOI:10.1016/j.pain.2006.01.027 · 5.84 Impact Factor
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    ABSTRACT: Sciatica in patients with disk disease was long ascribed to pressure put on the sciatic nerve root by a herniated disk. However, a role for chemical factors acting in conjunction with this mechanical insult is suggested by a number of clinical observations: disk surgery does not consistently provide pain relief, large disk herniations are not always symptomatic, severe pain may be present in patients without imaging evidence of nerve root compression, the severity of symptoms and neurological signs is not well correlated with the size of the disk herniation, and conservative therapy is often effective. Experimental studies have provided further evidence for a chemical component: disk herniations can undergo spontaneous resorption, the intervertebral disk is immunogenic, and mediators for inflammation have been identified within intervertebral disk tissue. The current pathophysiological theory incriminates proinflammatory substances secreted by the nucleus pulposus (NP). When preexisting or concomitant mechanical injury to a nerve root occurs, these substances can cause nerve root pain. Animal experiments have established that the NP can induce functional and structural nerve root abnormalities in the absence of mechanical compression and that this effect is mediated by substances located at the surface of NP cells. Methylprednisolone, diclofenac, indomethacin, doxycycline, and cyclosporine induce variable inhibition of this effect. Available information points to tumor necrosis factor-alpha (TNF-alpha) as the main candidate among substances potentially responsible for nerve root pain. Therefore, trials of TNF-alpha antagonists in patients with disk-related sciatica are warranted.
    Joint Bone Spine 04/2006; 73(2):151-8. DOI:10.1016/j.jbspin.2005.03.003 · 3.22 Impact Factor
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FGFR3 and TP53 mutation analysis in inverted urothelial papilloma: incidence and etiological considerations

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Modern Pathology (Impact Factor: 6.36). 03/2009; 22(5):627-632. DOI: 10.1038/modpathol.2009.28

ABSTRACT Urothelial papillomas and low-grade urothelial carcinomas have shown a high incidence of fibroblast growth factor receptor 3 (FGFR3) mutations and are associated with a favorable prognosis. The association of FGFR3 mutations with inverted papillomas is less known. We analyzed 20 cases of inverted papilloma in the urinary tract. Mutations of FGFR3 (exons 7, 10, and 15) and TP53 genes were evaluated by DNA sequencing in these cases. Point mutations of the FGFR3 gene were identified in 45% (9 of 20) of inverted papillomas with four cases exhibiting mutations at multiple exons. Seven cases had exon 7 mutations containing R248C, S249T, L259L, P260P, and V266M. Two cases had exon 10 and 15 mutations including A366D, H412H, E627D, D641N, and H643D; five cases had N653H. The most frequent mutation was identified at R248C. None of the inverted papillomas exhibited mutations in TP53. During a mean follow-up of 78 months, none had recurrence or developed urothelial carcinoma. These findings support the concept that low-grade and low-stage urothelial neoplasms arise in a background of molecular changes that are distinctly different from the molecular changes of high-grade and high-stage urothelial cancers.Keywords: urinary bladder, urinary tract, inverted papilloma, fibroblast growth factor receptor 3, tumorigenesis, TP mutations

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Involvement of Inferior Parietal Lobules in Prospective Memory Impairment during Acute MDMA (Ecstasy) Intoxication: An Event-Related fMRI Study

Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.83). 06/2009; 34(7):1641-8. DOI: 10.1038/npp.2008.219
Source: PubMed

ABSTRACT Prospective memory refers to the realization of delayed intentions. Several studies have shown that 3,4-methylenedioxy-methamphetamine (MDMA) users perform worse on measures of prospective memory as compared to nondrug users. Interpretation of these data may be limited because of polydrug use, psychosocial stressors, and increased psychopathology that have been reported in MDMA users. This study was designed to directly assess the pharmacological effect of MDMA on prospective memory and brain activity in a double-blind, placebo-controlled, cross-over study. Twelve recreational MDMA users received MDMA 75 mg and placebo and performed an objective prospective memory task during functional imaging. During prospective memory task performance subjects were engaged in a foreground task that consisted of a simple reaction time to visual stimuli (Go trials) and a prospective task of withholding a response during trials that were part of a dynamic memory set (No go trials). Behavioral data showed that a single dose of MDMA increased prospective memory failures in the No go trials, and that number of prospective memory failures was positively correlated to MDMA concentration in plasma. Functional imaging showed that MDMA decreased BOLD activation during Go trials in the thalamus (left), putamen (left), precuneus (left), and the inferior parietal lobules (bilateral), as compared to placebo. During No go trials, MDMA reduced BOLD deactivation in the inferior parietal lobules (bilateral), as compared to placebo. It is concluded that the loss of deactivation in inferior parietal lobules may account for increments in memory failures observed during MDMA intoxication.

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Available from: Kim P. C. Kuypers, Jan 16, 2015
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    ABSTRACT: 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.
    The International Journal of Neuropsychopharmacology 12/2013; 17(04):1-14. DOI:10.1017/S1461145713001405 · 5.26 Impact Factor
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    ABSTRACT: BACKGROUND: Ecstasy use is commonly linked with memory deficits in abstinent ecstasy users. Similar impairments are being found during ecstasy intoxication after single doses of MDMA. The concordance of memory impairments during intoxication and abstinence suggests a similar neuropharmacological mechanism underlying acute and chronic memory impairments. The mechanism underlying this impairment is to date not known. We hypothesized that cortisol might play an important role in this mechanism as cortisol, implicated in the regulation of memory performance, can be brought out of balance by stressors like MDMA. METHODS: In the present study we aimed to block the MDMA-induced acute memory defect by giving participants a cortisol synthesis inhibitor (Metyrapone) together with a single dose of MDMA. Seventeen polydrug MDMA users entered this placebo controlled within subject study with four treatment conditions. The treatments consisted of MDMA (75 mg) and Metyrapone (750mg), alone and in combination, and double placebo. Pre-treatment with Metyrapone or Placebo occurred 1h prior to MDMA or Placebo administration. Memory performance was tested at peak drug concentrations by means of several memory tests. Cortisol levels were determined in blood and oral fluid; this served as a control measure to see whether manipulations were effective. RESULTS: Main findings indicated that whereas treatment with Metyrapone blocked the expected MDMA-induced increase in cortisol levels in blood, it did not prevent the MDMA-induced memory deficit from happening. CONCLUSION: We therefore conclude that MDMA-induced increments in cortisol concentrations are not related to MDMA-induced memory impairments.
    British Journal of Pharmacology 09/2012; 168(3). DOI:10.1111/j.1476-5381.2012.02196.x · 4.99 Impact Factor
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    ABSTRACT: In this issue of the BJP, Green et al. suggest that animal data could not be used to predict the adverse effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans and that MDMA did not produce 5-HT neurotoxicity in the human brain. This proposal was, however, not accompanied by a review of the empirical evidence in humans. The neuroimaging data on 5-HT markers in abstinent recreational ecstasy/MDMA users are extensive and broadly consistent. Reduced levels of the 5-HT transporter (SERT) have been found by research groups worldwide using a variety of assessment measures. These SERT reductions occur across the higher brain regions and remain after controlling for potential confounds. There are also extensive empirical data for impairments in memory and higher cognition, with the neurocognitive deficits correlating with the extent of SERT loss. Hence, MDMA is clearly damaging to humans, with extensive empirical data for both structural and functional deficits.
    British Journal of Pharmacology 03/2012; 166(5):1518-20; discussion 1521-2. DOI:10.1111/j.1476-5381.2012.01941.x · 4.99 Impact Factor


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Amygdala and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents With Generalized Anxiety Disorder

Department of Psychology, University of Michigan, 530 Church St, Ann Arbor, MI 48109-1043, USA.
Archives of general psychiatry (Impact Factor: 13.75). 06/2008; 65(5):568-76. DOI: 10.1001/archpsyc.65.5.568
Source: PubMed

ABSTRACT Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly presented threats in GAD or in pediatric anxiety.
To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD.
Case-control study.
Government clinical research institute.
Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis.
We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces.
When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects.
Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.

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Available from: Brendan Patrick Bradley, Jun 25, 2015
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    ABSTRACT: Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. © 2014 Wiley Periodicals, Inc. Dev Psychobiol
    Developmental Psychobiology 12/2014; 56(8). DOI:10.1002/dev.21260 · 3.16 Impact Factor
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    ABSTRACT: B*ACKGROUND: It is established that pediatric patients with generalized anxiety disorder (GAD) exhibit functional abnormalities and altered gray matter volumes in neural structures that subserve emotional processing, yet there are no data regarding the surface anatomy of the cerebral cortex in youth with GAD. METHODS: Using an automated surface-based approach (FreeSurfer), cortical thickness was assessed node-by-node over the entire cerebral cortex in adolescents with GAD and no co-occurring major depressive disorder (n = 13) and healthy subjects (n = 19). RESULTS: Compared with healthy adolescents, youth with GAD exhibited increased cortical thickness in the right inferolateral and ventromedial prefrontal cortex (i.e., inferior frontal gyrus), the left inferior and middle temporal cortex as well as the right lateral occipital cortex. No relationships were observed between cortical thickness and the severity of anxiety symptoms in the significant regions that were identified in the vertex-wise analysis. CONCLUSIONS: These findings suggest abnormalities in adolescents with GAD in cortical thickness in an ensemble of regions responsible for fear learning, fear extinction, reflective functioning (e.g., mentalization), and regulation of the amygdala.
    Journal of Anxiety Disorders 10/2014; 28(7). DOI:10.1016/j.janxdis.2014.07.012 · 2.96 Impact Factor
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    ABSTRACT: Cognitive processing biases, such as increased attention to threat, are gaining recognition as causal factors in anxiety. Yet, little is known about the anatomical pathway by which threat biases cognition and how genetic factors might influence the integrity of this pathway, and thus, behavior. For 40 normative adults, we reconstructed the entire amygdalo-prefrontal white matter tract (uncinate fasciculus) using diffusion tensor weighted MRI and probabilistic tractography to test the hypothesis that greater fiber integrity correlates with greater nonconscious attention bias to threat as measured by a backward masked dot-probe task. We used path analysis to investigate the relationship between brain-derived nerve growth factor genotype, uncinate fasciculus integrity, and attention bias behavior. Greater structural integrity of the amygdalo-prefrontal tract correlates with facilitated attention bias to nonconscious threat. Genetic variability associated with brain-derived nerve growth factor appears to influence the microstructure of this pathway and, in turn, attention bias to nonconscious threat. These results suggest that the integrity of amygdalo-prefrontal projections underlie nonconscious attention bias to threat and mediate genetic influence on attention bias behavior. Prefrontal cognition and attentional processing in high bias individuals appear to be heavily influenced by nonconscious threat signals relayed via the uncinate fasciculus.
    Cerebral Cortex 09/2014; 24(9):2249-2257. DOI:10.1093/cercor/bht089 · 8.31 Impact Factor


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Do quality improvement organizations improve the quality of hospital care for Medicare beneficiaries?

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 06/2005; 293(23):2900-7. DOI: 10.1001/jama.293.23.2900
Source: PubMed

ABSTRACT Quality improvement organizations (QIOs) are charged with improving the quality of medical care for Medicare beneficiaries.
To explore whether the quality of hospital care for Medicare beneficiaries improves more in hospitals that voluntarily participate with Medicare's QIOs compared with nonparticipating hospitals. DESIGN, SETTING, AND DATA: Data from 4 QIOs charged with improving the quality of care in 5 states (Maryland, Nevada, New York, Utah, and Washington) and the District of Columbia were used. Hospitals participate with the QIOs on quality improvement on a voluntary basis. A retrospective study was conducted comparing improvement in the quality of care of patients in hospitals that actively participated with the QIOs vs hospitals that did not. The medical records of approximately 750 Medicare beneficiaries per state in each of 5 clinical areas (atrial fibrillation, acute myocardial infarction, heart failure, pneumonia, and stroke) were abstracted at baseline (1998) and follow-up (2000-2001).
Fifteen quality indicators associated with improved outcomes in the prevention or treatment of the 5 clinical areas were used as quality of care measures. These 15 indicators were specifically targeted by the QIOs for quality improvement during the study period.
Hospitals that voluntarily participate with the QIOs are more likely to be larger than nonparticipating hospitals (P<.05). At baseline, there were statistically significant (P<.05) differences between participating and nonparticipating hospitals on 5 of 15 quality indicators, with participating hospitals performing better on 3 of 5. There was no statistically significant difference in change from baseline to follow-up between participating and nonparticipating hospitals on 14 of 15 quality indicators. The one exception was that participating hospitals improved more on the pneumonia immunization indicator than nonparticipating hospitals (P = .005).
Hospitals that participate with the QIO program are not more likely to show improvement on quality indicators than hospitals that do not participate.

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    ABSTRACT: Racial and ethnic minorities bear a disproportionate burden of the diabetes epidemic; they have higher prevalence rates, worse diabetes control, and higher rates of complications. This article reviews the effectiveness of health care interventions at improving health outcomes and/or reducing diabetes health disparities among racial/ethnic minorities with diabetes. Forty-two studies met inclusion criteria. On average, these health care interventions improved the quality of care for racial/ethnic minorities, improved health outcomes (such as diabetes control and reduced diabetes complications), and possibly reduced health disparities in quality of care. There is evidence supporting the use of interventions that target patients (primarily through culturally tailored programs), providers (especially through one-on-one feedback and education), and health systems (particularly with nurse case managers and nurse clinicians). More research is needed in the areas of racial/ethnic minorities other than African Americans and Latinos, health disparity reductions, long-term diabetes-related outcomes, and the sustainability of health care interventions over time.
    Medical Care Research and Review 11/2007; 64(5 Suppl):101S-56S. DOI:10.1177/1077558707305409 · 2.57 Impact Factor
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    ABSTRACT: The 1965 legislation that established Medicare and Medicaid declared that the Federal Government would not interfere in clinical medicine. Despite the original intent, Medicare and Medicaid have had tremendous influence on medical practice. In this article, we focus on four policy areas that illustrate the influence of CMS (and its predecessor agencies) on medical practice. We discuss the implications of the relationship between CMS and clinical medicine and how this relationship has changed over time. We conclude with thoughts about potential future efforts at CMS.
    Health care financing review 01/2005; 27(2):79-90. · 2.06 Impact Factor
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    ABSTRACT: The US healthcare system provides evidence that spending more on healthcare does not result in better care, but also offers many lessons and surprises on how the quality and safety of healthcare can be improved. The US Institute of Medicine has clearly articulated what needs to be achieved. A series of US agencies, including the Joint Commission on Accreditation of Healthcare Organizations, the Centers for Medicare and Medicaid Services (CMS), other major players, and the Hospital Quality Alliance, routinely collect and report on numerous measures of the quality and safety of inpatient and outpatient healthcare. Most attention to improving care in the UK has focused on vertically integrated, closed healthcare systems, but the US experience provides additional models from the work of Quality Improvement Organizations and of numerous voluntary organisations that sponsor collaborative improvement.
    Clinical medicine (London, England) 11/2006; 6(6):551-8. DOI:10.7861/clinmedicine.6-6-551 · 1.69 Impact Factor

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Weiliam Chen

CUNY Graduate Center, New York, New York, United States

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Publications (47)188.65 Total impact

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    ABSTRACT: Despite the prevalence of disc degeneration and its contributions to low back problems, many current treatments are palliative only and ultimately fail. To address this, nucleus pulposus replacements are under development. Previous work on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean has shown that it has properties similar to native nucleus pulposus, can restore compressive range of motion in ovine discs, is biocompatible, and promotes cell proliferation. The objective of this study was to determine if the hydrogel implant will be contained and if it will restore mechanics in human discs undergoing physiologic cyclic compressive loading. Fourteen human lumbar spine segments were tested using physiologic cyclic compressive loading while intact, following nucleotomy, and again following treatment of injecting either PBS (sham, n=7) or hydrogel (implant, n=7). In each compressive test, mechanical parameters were measured immediately before and after 10,000 cycles of compressive loading and following a period of hydrated recovery. The hydrogel implant was not ejected from the disc during 10,000 cycles of physiological compression testing and appeared undamaged when discs were bisected following all mechanical tests. For sham samples, creep during cyclic loading increased (+15%) from creep during nucleotomy testing, while for implant samples creep strain decreased (-3%) toward normal. There was no difference in compressive modulus or compressive strains between implant and sham samples. These findings demonstrate that the implant integrates sufficiently with the disc tissue to prevent expulsion over 10,000 cycles of compressive loading and preserves disc creep within human L5-S1 discs. This and previous studies provide a solid foundation for continuing to evaluate the efficacy of the hydrogel implant.
    Journal of Biomechanical Engineering 05/2015; DOI:10.1115/1.4030530 · 1.75 Impact Factor
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    ABSTRACT: Intervertebral disc degeneration is implicated as a major cause of low back pain. There is a pressing need for new regenerative therapies for disc degeneration that restore native tissue structure and mechanical function. To that end we investigated the therapeutic potential of an injectable, triple interpenetrating network hydrogel comprised of dextran, chitosan and teleostean, for functional regeneration of the nucleus pulposus of the intervertebral disc in a series of biomechanical, cytotoxicity and tissue engineering studies. Biomechanical properties were evaluated as a function of gelation time, with the hydrogel reaching ~90% of steady-state aggregate modulus within 10 hours. Hydrogel mechanical properties evaluated in confined and unconfined compression were comparable to native human NP properties. To confirm containment within the disc under physiological loading, toluidine blue labeled hydrogel was injected into human cadaveric spine segments after creation of a nucleotomy defect, and the segments were subjected to 10,000 cycles of loading. Gross analysis demonstrated no implant extrusion, and further, that the hydrogel interdigitated well with native NP. Constructs were next surface-seeded with NP cells and cultured for 14 days, confirming lack of hydrogel cytotoxicity, with the hydrogel maintaining NP cell viability and promoting proliferation. Next, to evaluate the potential of the hydrogel to support cell-mediated matrix production, constructs were seeded with mesenchymal stem cells (MSCs) and cultured under pro-chondrogenic conditions for up to 42 days. Importantly, the hydrogel maintained MSC viability and promoted proliferation, as evidenced by increasing DNA content with culture duration. MSCs differentiated along a chondrogenic lineage, evidenced by up-regulation of aggrecan and collagen II mRNA, and increased GAG and collagen content, and mechanical properties with increasing culture duration. Collectively, these results establish the therapeutic potential of this novel hydrogel for functional regeneration of the NP. Future work will confirm the ability of this hydrogel to normalize the mechanical stability of cadaveric human motion segments, and advance the material towards human translation using preclinical large animal models.
    Tissue Engineering Part A 01/2014; DOI:10.1089/ten.TEA.2013.0516 · 4.64 Impact Factor
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    ABSTRACT: BACKGROUND: Pathologic analysis of deep tissue obtained during debridement of venous ulcers is often unnoticed in its importance. We previously reported pathologic findings on 139 patients with venous ulcers. The objective of this study was to correlate the pathologic findings in venous ulcers with wound healing to establish a negative margin for debridement. STUDY DESIGN: Consecutive patients with a lower extremity venous ulcer present for at least 4 weeks, presenting to a single wound healing center, were included. Wounds underwent aggressive surgical debridement beyond the subcutaneous level until judged to have a viable base. Specimens were scored based on cellularity, vascularity, collagen composition, inflammation, and dense fibrosis, with a highest possible score of 13. Healing was the primary outcome for analysis. RESULTS: Of the 26 patients who met inclusion criteria, only 50% of them (13 patients) with a total of 18 venous ulcers underwent surgical debridement available for pathologic analysis. Mean ulcer area was 34.7 cm(2) at initial presentation, and 89% of patients had a continuous positive healing curve as measured by decreasing wound area (from 34.7 cm(2) to 14.3 cm(2)). However, specimens with dense fibrosis, decreased cellularity, mature collagen, and pathology score less than 10 were predominantly nonhealing ulcers. CONCLUSIONS: Presence of dense fibrosis and high levels of mature collagen in deep tissue specimens are significant correlative factors in nonhealing of venous ulcers. We recommend deep debridement on all venous ulcers that are refractory to healing until the level of absence of dense fibrosis and mature collagen is reached to promote venous ulcer healing.
    Journal of the American College of Surgeons 09/2012; 215(6). DOI:10.1016/j.jamcollsurg.2012.08.008 · 4.45 Impact Factor
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    ABSTRACT: Investigation of injectable nucleus pulposus (NP) implant. To assess the ability of a recently developed injectable hydrogel implant to restore nondegenerative disc mechanics through support of NP functional mechanics. Although surgical intervention for low back pain is effective for some patients, treated discs undergo altered biomechanics and adjacent levels are at increased risk for accelerated degeneration. One potential treatment as an alternative to surgery for degenerated disc includes the percutaneous delivery of agents to support NP functional mechanics. The implants are delivered in a minimally invasive fashion, potentially on an outpatient basis, and do not preclude later surgical options. One of the challenges in designing such implants includes the need to match key NP mechanical behavior and mimic the role of native nondegenerate NP in spinal motion. The oxidized hyaluronic acid gelatin implant material was prepared. In vitro mechanical testing was performed in mature ovine bone-disc-bone units in 3 stages: intact, discectomy, and implantation versus sham. Tested samples were cut axially for qualitative structural observations. Discectomy increased axial range of motion (ROM) significantly compared with intact. Hydrogel implantation reduced ROM 17% (P < 0.05) compared with discectomy and returned ROM to intact levels (ROM intact 0.71 mm, discectomy 0.87 mm, postimplantation 0.72 mm). Although ROM for the hydrogel implant group was statistically unchanged compared with the intact disc, ROM for sham discs, which received a discectomy and no implant, was significantly increased compared with intact. The compression and tension stiffness were decreased with discectomy and remained unchanged for both implant and sham groups as expected because the annulus fibrosus was not repaired. Gross morphology images confirmed no ejection of NP implant. An injectable implant that mimics nondegenerate NP has the potential to return motion segment ROM to normal subsequent to injury.
    Spine 05/2012; 37(18):E1099-105. DOI:10.1097/BRS.0b013e31825cdfb7 · 2.45 Impact Factor
  • Huijuan Liao, Irena Pastar, Weiliam Chen
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    ABSTRACT: Utilizing a three-dimensional in vitro glycated collagen model, we evaluated the therapeutic effects of a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone, and its potential as a topical treatment of diabetic chronic wounds. Rosiglitazone induced fibroblast migration, α-smooth muscle actin production, and transformation into myofibroblasts in the presence of advanced glycation end products. Both transforming growth factor β and peroxisome proliferator-activated receptor-γ expression were induced, while the receptor for advanced glycation end products was suppressed. Lastly, the reduced activities of matrix metalloproteinase-2 and matrix metalloproteinases-9 in the carboxymethyllysine-modified collagen matrices by rosiglitazone increases extracellular matrix deposition. Our findings identify rosiglitazone as a candidate for localized topical treatment of diabetic chronic wounds.
    Wound Repair and Regeneration 05/2012; 20(3):435-43. DOI:10.1111/j.1524-475X.2012.00795.x · 2.77 Impact Factor
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    ABSTRACT: Diabetic foot ulcers (DFUs) are a significant and rapidly growing complication of diabetes and its effects on wound healing. Over half of diabetic patients who develop a single ulcer will subsequently develop another ulcer of which the majority will become chronic non-healing ulcers. One-third will progress to lower extremity amputation. Over the past decade, the outcomes for patients with DFUs ulcers have not improved, despite advances in wound care. Successful treatment of diabetic foot ulcers is hindered by the lack of targeted therapy that hones in on the healing processes dysregulated by diabetes. Stem cells are a promising treatment for DFUs as they are capable of targeting, as well as bypassing, the underlying abnormal healing mechanisms and deranged cell signaling in diabetic wounds and promote healing. This review will focus on existing stem cell technologies and their application in the treatment of DFUs.
    Diabetes research and clinical practice 12/2011; 96(1):1-9. DOI:10.1016/j.diabres.2011.10.032 · 2.54 Impact Factor
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    ABSTRACT: Fibroblasts and macrophages are the two major types of cells responding to implanted biomaterials. They play crucial roles in inflammatory responses, host-material interactions and tissue remodeling. However, the synergistic interactions of these two cell types with biomaterials are not fully understood. In this investigation, an in vitro fibroblast/macrophage co-culture system was utilized to examine the biocompatibility and the potential to induce inflammatory responses of an electrospun Dextran/PLGA scaffold. The scaffold did not affect the morphologies, attachments, proliferations and viabilities of both the fibroblasts and macrophages, cultured separately or together. Moreover, it only activated a small subset of the macrophages implicating a low potential to induce either severe acute or chronic inflammatory response. Additionally, fibroblasts played a role in prolonging macrophage activation in the presence of the scaffolds. Using antibody arrays, IL-10, SDF-1, MIP-1 gamma and RANTES were found to be up-regulated when the cells were incubated with the scaffolds. The results of subdermal implantation of the Dextran/PLGA scaffolds confirmed its biocompatibility and low inflammatory potential.
    Biomedical Materials 12/2011; 6(6):065002. DOI:10.1088/1748-6041/6/6/065002 · 2.92 Impact Factor
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    ABSTRACT: Hydroxyurea (HU) has been shown to induce a variety of cutaneous adverse reactions, including severe leg ulcers. This report shows a successful treatment of a HU-induced chronic wound associated with squamous cell carcinomas (SCC). A 62-year-old patient affected with polycythemia vera and treated with HU for 10 years, presented with a non healing ulcer on a left heel. The patient gave a history of suffering from the wound for over 2 years. Biopsy showed evidence of invasive SCC. The patient underwent Mohs surgery and a greater saphenous vein ablation for polycythemia vera-associated vascular complications. The wound consistently decreased in size following successive debridements and coverage with human skin equivalent. The wound healed completely after a 6-month period. A multidisciplinary team approach to the treatment proved to be effective resulting in healing of this multifactorial chronic ulcer.
    International Wound Journal 11/2011; 9(3):324-9. DOI:10.1111/j.1742-481X.2011.00887.x · 2.02 Impact Factor
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    ABSTRACT: The objective of the study was to inform wound care practitioners of mesenchymal stem cell application for nonhealing wounds. Recent advances in delivery systems are also discussed in order to highlight potential improvements toward clinical application of stem cell therapy for chronic wounds. MEDLINE and PubMed Central were searched for scientific studies regarding the use of mesenchymal stem cells and delivery systems in wound healing. Preclinical studies using stem cells as therapeutic modality for chronic wounds were selected for this review. Information on study design, sample size and characteristics, stem cell source, type of delivery systems, and rate and time of wound closure was abstracted. Application of mesenchymal stem cells improved wound healing in experimental and clinical settings. Advances in stem cell therapy and delivery vehicles offer promising alternatives to current limited therapeutic modalities for chronic wounds. Stem cell therapy has recently emerged as a promising therapeutic strategy for nonhealing wounds. Further research is needed to evaluate the relationship between the various delivery systems and stem cells in order to maximize their therapeutic effects. Development of novel delivery vehicles for stem cells can open new opportunities for more effective cell therapy of chronic wounds.
    Advances in skin & wound care 11/2011; 24(11):524-32; quiz 533-4. DOI:10.1097/01.ASW.0000407648.89961.a6 · 1.63 Impact Factor
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    ABSTRACT: A microfluidic emulsification method for producing monodispersed microgels from a triple interpenetrating network (3XN) hydrogel was reported. This 3XN system is comprised of minimally modified natural GRAS materials, partially oxidized dextran (Odex), Teleostean, and N-carboxyethyl chitosan (CEC), without the need of utilizing extraneous crosslinkers or photo-initiators, which has been proved to be a novel biodegradable and mechanically strong in-situ gelable hydrogel systems. A microfluidic chip was specifically designed to produce microgels from the 3XN hydrogel system. The study shows that microfluidic emulsification method could yield microgels with better size and morphology than the conventional in-emulsion-crosslinking method, and the size of microgels could be modulated by simply adjusting the flow rates of the oil and/or the individual precursor fluids. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
    Journal of Applied Polymer Science 09/2011; 121(5):3093 - 3100. DOI:10.1002/app.34001 · 1.64 Impact Factor
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    Hanwei Zhang, Aisha Qadeer, Weiliam Chen
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    ABSTRACT: In situ gelable interpenetrating double-network hydrogels composed of thiolated chitosan (Chitosan-NAC) and oxidized dextran (Odex), completely devoid of potentially cytotoxic small molecule cross-linkers and that do not require complex maneuvers or catalysis, have been formulated. The interpenetrating network structure is created by Schiff base formations and disulfide bond inter-cross-linkings through exploiting the disparity of their reaction times. Compared with the autogelable thiolated chitosan hydrogels that typically require a relatively long time span for gelation to occur, the Odex/Chitosan-NAC composition solidifies rapidly and forms a well-developed 3D network in a short time span. Compared with typical hydrogels derived from natural materials, the Odex/Chitosan-NAC hydrogels are mechanically strong and resist degradation. The cytotoxicity potential of the hydrogels was determined by an in vitro viability assay using fibroblast as a model cell, and the results reveal that the hydrogels are noncytotoxic. In parallel, in vivo results from subdermal implantation in mice models demonstrate that this hydrogel is not only highly resistant to degradation but also induces very mild tissue response.
    Biomacromolecules 03/2011; 12(5):1428-37. DOI:10.1021/bm101192b · 5.79 Impact Factor
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    [Show abstract] [Hide abstract]
    ABSTRACT: An in situ gelable and biodegradable triple-interpenetrating network (3XN) hydrogel, completely devoid of potentially cytotoxic extraneous small molecule crosslinkers, is formulated from partially oxidized dextran (Odex), teleostean and N-carboxyethyl chitosan (CEC). Both the rheological profile and mechanical strength of the 3XN hydrogel approximate the combined characteristics of the three individual hydrogels composed of the binary partial formulations (i.e., Odex/CEC, Odex/teleostean, and CEC/teleostean). The 3XN hydrogel is considerably more resistant to fibroblast-mediated degradation compared to each partial formulation in cell culture models; this is attributable to the interpenetrating triple-network structure. The presence of teleostean in the 3XN hydrogel imparts cell affinity, constituting an environment amenable to fibroblast growth. in vivo subdermal injection into mouse model shows that the 3XN hydrogel does not induce extensive inflammatory response nor is there any evidence of tissue necrosis, further confirming the non-cytotoxicity of the hydrogel and its degradation byproducts. Importantly, the capability of the 3XN hydrogel to serve as a sustained drug delivery vehicle is confirmed using rosiglitazone as a model drug. The presence of rosiglitazone profoundly changes the cell/tissue interactions with the subdermally injected 3XN hydrogel. Rosiglitazone suppresses both the inflammatory response and tissue repair in a dose-dependent manner and considerably moderated the hydrogel degradation.
    Biomaterials 10/2010; 32(3):890-8. DOI:10.1016/j.biomaterials.2010.09.053 · 8.31 Impact Factor
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    Qiong Zeng, Weiliam Chen
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    ABSTRACT: Tissues/cells-mediated biodegradable material degradation is epitomized by the constantly changing tissues/cell-implant interface, implicating the constant adaptation of the tissues/cells. Macrophages and fibroblasts are multi-functional cells highly involved in the interactions; the two cell types modulates the behaviors of each other, but their combinatorial functional behavior in the presence of interactive bioactive wound dressings has not been adequately examined. The activity is further complicated by the implantation of biodegradable materials, such as hydrogels commonly utilized as wound dressings, in a pathological environment and this is exemplified by the macrophages with a diabetic pathology producing an alternative cytokine profile which is implicated in wound healing delay. In this study, an in situ gelable formable/conformable hydrogel formulated from modified alginate and marine gelatin was used as a model biodegradable interactive wound dressing to elucidate the combinatorial behavior of macrophages/fibroblasts derived from both normal and diabetic hosts. Cell proliferation, migration and distribution were first characterized; this was followed by simultaneous quantitative detection of 40 inflammatory cytokines and chemokines by a protein microarray. The results showed that the macrophages/fibroblasts co-culture promoted fibroblasts proliferation and migration in the presence of the hydrogel; moreover, the expressions of inflammatory cytokines and chemokines were altered when compared with the corresponding fibroblasts or macrophages monocultures. The inflammatory cytokines patterns between the normal and diabetic hosts were considerably different.
    Biomaterials 08/2010; 31(22):5772-81. DOI:10.1016/j.biomaterials.2010.04.022 · 8.31 Impact Factor
  • Hanwei Zhang, Huijuan Liao, Weiliam Chen
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    ABSTRACT: An in situ gelable glycation-resistant hydrogel has been prepared from oxidized alginate (Oalg) and gelatin. Aminoguanidine, an effective inhibitor of the glycation reaction, was first encapsulated in gelatin microspheres followed by incorporation into the hydrogel. The gelation process was monitored rheologically, and the results showed that the AMG-loaded Oalg/gelatin system solidified quickly at body temperature. Moreover, the hydrogels were highly porous, and the AMG-loaded microspheres dispersed in the hydrogels remained intact. Hydrogels' AMG loadings did not appear to change their degradation behaviors. AMG could be released from the hydrogels in a sustainable manner for a relatively short duration. Incorporation of AMG into the hydrogels resulted in imparting a glycation-resistant capability. Lastly, long-term in vitro incubation of all hydrogel formulations with fibroblasts did not reveal any cytotoxic potential.
    Journal of Biomaterials Science Polymer Edition 01/2010; 21(3):329-42. DOI:10.1163/156856209X415864 · 1.36 Impact Factor
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    ABSTRACT: Creating monodispersed hydrogel microparticles is advantageous for drug delivery applications. We explore microfluidic flow focusing as a method for generating such particles. Our hydrogel has a unique composition that makes it biodegradable and mechanically strong. We designed and manufactured a polymer microfluidic chip that mixes three viscous precursor solutions and generates a steady stream of microparticles from that solution. We found that microfluidic flow focusing produce particle with a coefficient of variance around 9%; this was a four times improvement over traditional methods.
    ASME 2010 8th International Conference on Nanochannels, Microchannels, and Minichannels collocated with 3rd Joint US-European Fluids Engineering Summer Meeting; 01/2010
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    ABSTRACT: Treatment of cerebral aneurysms by endovascular deployment of liquid embolic agents has been proposed as an alternative strategy to conventional coiling, and new materials are being developed for embolization. In this study, the authors used a single-injection, biocompatible, biodegradable and pH-responsive acrylated chitosan (aCHN) with conjugated vascular endothelial growth factor (rhVEGF) in a rat aneurysm model. The efficacy of the aCHN formulation with rhVEGF was tested using a common carotid artery occlusion model in rats, and the extent of embolization was evaluated using quantitative, qualitative, and histopathological techniques after 14 days of implantation. The mean occlusion was significantly greater for the rhVEGF/aCHN-treated group (96.8 +/- 3.0%) than for the group receiving aCHN (74.7 +/- 5.6%) (p < 0.01). Through qualitative evaluation, intimal and medial proliferation were significantly greater with rhVEGF/aCHN than with aCHN and controls (p < 0.001). Degradation of the aCHN filler was monitored in concert with the production of extracellular matrix components. Macrophages migrated in and proliferated inside the occluded carotid artery lumens were identified by histological and immunostainings. Results showed resorption of chitosan with concurrent development of collagen and elastin into the vessel lumen, suggesting clot maturation into fibrosis. Chitosan with a bioactive agent such as rhVEGF showed excellent results in occluding aneurysms in a rat model.
    Journal of Neurosurgery 08/2009; 112(3):658-65. DOI:10.3171/2009.1.JNS08411 · 3.15 Impact Factor
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    ABSTRACT: Closure of diabetic dermal chronic wounds remains a clinical challenge. Implant-assisted healing is emerging as a potential class of therapy for dermal wound closure; this advancement has not been paralleled by the development in complementary diagnostic techniques to objectively monitor the wound-healing process in conjunction with assessing/monitoring of implant efficacy. Biopsies provide the most objective morphological assessments of wound healing; however, they not only perpetuate the wound presence but also increase the risk of infection. A noninvasive and high-resolution imaging technique is highly desirable to provide objective longitudinal diagnosis of implant-assisted wound healing. We investigated the feasibility of deploying optical coherence tomography (OCT) for noninvasive monitoring of the healing of full-thickness excisional dermal wounds implanted with a novel in situ gelable hydrogel composed of N-carboxyethyl chitosan, oxidized dextran, and hyaluronan, in both normal and db/db mice. The results showed that OCT was able to differentiate the morphological differences (e.g., thickness of dermis) between normal and diabetic mice as validated by their corresponding histological evaluations (p < 0.05). OCT could detect essential morphological changes during wound healing, including re-epithelization, inflammatory response, and granulation tissue formation as well as impaired wound repair in diabetic mice. Importantly, by tracking specific morphological changes in hydrogel-assisted wound healing (e.g., implants' degradation and resorption, cell-mediated hydrogel degradation, and accelerated re-epithelization), OCT could also be deployed to monitor and evaluate the transformation of implanted biomaterials, thus holding the promise for noninvasive and objective monitoring of wound healing longitudinally and for objective efficacy assessment of implantable therapeutics in tissue engineering.
    Tissue Engineering Part C Methods 07/2009; 16(2):237-47. DOI:10.1089/ten.TEC.2009.0152 · 4.64 Impact Factor
  • Source
    Huijuan Liao, Julia Zakhaleva, Weiliam Chen
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    ABSTRACT: Dermal accumulation of advanced glycation end products (AGEs) has increasingly been implicated as the underlying cause of delayed diabetic wound healing. Devising an in vitro model to adequately mimic glycated tissues will facilitate investigation into the mechanism of glycation in conjunction with exploration of new approaches or improvement of current therapies for treating diabetic chronic wounds. Collagen matrices were artificially glycated and the presence of AGEs was demonstrated by immunostaining. Both the mechanical properties of the collagen matrices and their interactions with fibroblasts (morphology, attachment, proliferation, and migration) were altered after glycation, moreover, there was evidence of impairment on extracellular matrix (ECM) remodeling as well as inhibition of cell-induced material contraction. The actin cytoskeletons of the fibroblasts residing in the glycated collagen matrices were reorganized. In vivo mice full-thickness dermal wound models implanted with glycated collagen matrices showed delayed wound healing response. Thus, the glycated collagen matrix is an adequate in vitro model to mimic glycated tissues and could serve as a facile experimental tool to investigate the mechanism of glycation in conjunction with exploration of new approaches or improvement of current therapies for treating diabetic wounds.
    Biomaterials 02/2009; 30(9):1689-96. DOI:10.1016/j.biomaterials.2008.11.038 · 8.31 Impact Factor
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    ABSTRACT: One mechanism that contributes to cerebral vasospasm is the impairment of potassium channels in vascular smooth muscles. Adenosine triphosphate-sensitive potassium channel openers (PCOs) appear to be particularly effective for dilating cerebral arteries in experimental models of subarachnoid hemorrhage (SAH). A mode of safe administration that provides timed release of PCO drugs is still a subject of investigation. The authors tested the efficacy of locally delivered intrathecal cromakalim, a PCO, incorporated into a controlled-release system to prevent cerebral vasospasm in a rat model of SAH. Cromakalim was coupled to a viscous carrier, hyaluronan, 15% by weight. In vitro release kinetics studies showed a steady release of cromakalim over days. Fifty adult male Sprague-Dawley rats weighing 350-400 g each were divided into 10 groups and treated with various doses of cromakalim or cromakalim/hyaluronan in a rat double SAH model. Treatment was started 30 minutes after the second SAH induction. Animals were killed 3 days after treatment, and the basilar arteries were processed for morphometric measurements and histological analysis. Controlled release of cromakalim from the cromakalim/hyaluronan implant at a dose of 0.055 mg/kg significantly increased lumen patency in a dose-dependent manner up to 94 +/- 8% (mean +/- standard error of the mean) of the basilar arteries of the sham group compared with the empty polymer group (p = 0.006). Results in the empty polymer group were not different from those in the SAH-only group, with a lumen patency of 65 +/- 12%. Lumen patencies of the cromakalim-only groups did not differ in statistical significance at low (64 +/- 9%) or high (66 +/- 7%) doses compared to the SAH-only group. Treatment of SAH with a controlled-release cromakalim/hyaluronan implant prevented experimental cerebral vasospasm in this rat double hemorrhage model; this inhibition was dose-dependent. The authors' results confirm that sustained delivery of cromakalim perivascularly to cerebral vessels could be an effective therapeutic strategy in the treatment of cerebral vasospasm after SAH.
    Journal of Neurosurgery 02/2009; 110(5):1015-20. DOI:10.3171/2008.8.JNS08202 · 3.23 Impact Factor
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    ABSTRACT: Microspheres formulated from blending poly(lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-grafted-chitosan (PEG-g-CHN), using a modified in-emulsion-solvent-evaporation method, were investigated for the delivery of protein. A model protein, bovine serum albumin (BSA), was incorporated into the PLGA/PEG-g-CHN microspheres and both initial burst and release kinetics could be modulated by varying the PEG-g-CHN content. Basic fibroblast growth factor (bFGF) was formulated into the microspheres containing 5% PEG-g-CHN and the bFGF contents in the releasates were determined by a receptor-based ELISA with their in vitro bioactivities validated by fibroblast cell culture. The in vivo effect of the bFGF microspheres formulation was evaluated in a hamster cheek pouch model using a 7 day exposure (e.g., before significant vascular remodeling was expected). Using intravital microscopy, the tissue showed no evidence of inflammation with any formulation; deliberate activation of a preconditioning response linked to inflammation was attenuated by BSA microspheres alone. Vasoactive responses (receptor-dependant and independent constriction and dilation) linked to nitric oxide were attenuated, and constriction to endothelin was enhanced in bFGF and not BSA containing microspheres. PLGA/PEG-g-CHN blended microspheres were also demonstrated to be non-inflammatory and non-thrombogenic in vivo by observing the vascular changes in the cheek pouch. In conclusion, the addition of PEG-g-CHN to PLGA microspheres can serve as a sustained delivery vehicle for bFGF and the released protein provides vasoactive changes consistent with chronic bFGF exposure.
    Journal of Biomaterials Science Polymer Edition 02/2009; 20(7-8):903-22. DOI:10.1163/156856209X444330 · 1.36 Impact Factor

Publication Stats

1k Citations
188.65 Total Impact Points

  • 2011–2014
    • CUNY Graduate Center
      New York, New York, United States
    • Tufts University
      • Department of Medicine
      Medford, MA, United States
  • 2011–2012
    • NYU Langone Medical Center
      • Department of Surgery
      New York, New York, United States
  • 2004–2010
    • Stony Brook University
      • Department of Biomedical Engineering
      Stony Brook, New York, United States
  • 2004–2008
    • State University of New York
      New York City, New York, United States


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Director jobs

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Found 83 Full Time jobs

  • /Research Director

    Singapore £3828.92-5264.77 per month Aspire

    Are you a Qualitative researcher who loves people and their idiosyncrasies?

    • 14 days ago
  • Head of Analytics

    Singapore £3828.92-5743.39 per month Aspire

    Are you a visionary who is looking for the next step up? As a leader in social media analytics, you will be someone who goes beyond the role, who i...

    • 14 days ago
  • Associate Director/Research Director - Boutique Integrated Agency

    London (Central), London (Greater) c.£60,000 + bonus and benefits Spalding Goobey Associates

    Every so often an agency breaks through the mould and enjoys real success born out of their point of difference and after three full years of consi...

    • 16 days ago
  • Research Director - Qualitative - Consumer, Media

    London £60000-80000 per annum Resources Group

    A great opportunity for a senior level researcher to join a highly regarded agency that attracts talented researchers from a range of career backgr...

    • 16 days ago
  • Media Business Lead, APAC

    Singapore £4307.54-5264.77 per month Aspire

    This global media planning and buying agency has an impressive lineup of blue chip, IT and B2B software clients. This agency has the feel of a smal...

    • 16 days ago
  • Insight Director - Leading Communications Agency (Contract)

    City of London £55-70 per annum Elizabeth Norman International

    An amazing opportunity to work in a highly prestigious and well established Communications Agency that specialise in PR, insights and strategic pla...

    • 17 days ago
  • Qualitative Director - Consultancy

    Central London £55-70,000 + benefits Spalding Goobey Associates

    As a talented senior qualitative practitioner, your career destinations are manifold. If the world of insight, innovation, brand strategy and desig...

    • 17 days ago
  • Director - Brand and Communications

    Central London £55-70,000 plus benefits Spalding Goobey Associates

    Our client's brand and advertising unit works with some of the leading consumer brands and companies in the world. Providing them not only with the...

    • 17 days ago
  • Research Director (Qualitative/ Mixed Methods) - Branding Research Consultancy

    London £55000-65000 per annum Resources Group

    An experienced research specialist with a qualitative or mixed methods background is eagerly sought by this highly regarded branding research consu...

    • 17 days ago
  • Research Director - International Research

    London £56000-65000 per annum Hasson Associates

    A small but growing team within a full service, global research agency are seeking a genuine FMCG ad hoc research specialist to join them.

    • 17 days ago
  • Quant Insight director | Research consultancy | Leeds

    Leeds £70000-100000 per annum Elizabeth Norman International

    Looking to work for a growing, sharp minded and fun research consultancy, who are compiled of some of the best senior research talent around? Want ...

    • 18 days ago
  • Insight Director - Qualitative - Global Brand Consultancy

    City of London £60000-75000 per annum Elizabeth Norman International

    Do you want to work for one of the most creative and well known Advertising & Brand agencies in the world? We are looking for an accomplished quali...

    • 18 days ago
  • Head of research | Global Brand consultancy

    London £60000-80000 per annum Elizabeth Norman International

    We're working with a highly successful brand consultancy who are looking to appoint a brand new head of research in their London office. With 6 off...

    • 18 days ago
  • Innovation/Strategy Directors-International Brand Consultancy

    London £65000-100000 per annum Elizabeth Norman International

    Innovation and Strategy director for a rapidly growing international Brand Consultancy

    • 18 days ago
  • Senior Director with Behavioural Economics Consultancy

    Shànghǎi £100000-125000 per annum Elizabeth Norman International

    An opportunity for an ambitious and experienced Qualitative Research Director to join an award-winning, boutique global agency in their Shanghai of...

    • 18 days ago
  • Star Associate to Director, Quant - Boutique Consultancy

    London (Central), London (Greater) £50-80,000 + benefits Spalding Goobey Associates

    This is a brilliant opportunity for an experienced quant AD or Director who has the enthusiasm, drive and brainpower to join and succeed in this sm...

    • 21 days ago
  • Director, Qualitative - UK and International

    Central London Outstanding package Spalding Goobey Associates

    Career defining role within the qual practice of a global research consultancy that enjoys roster relationships with the world's best clients.

    • 21 days ago
  • Consumer Insight Director - Major Agency

    London £40-44,000 + benefits Spalding Goobey Associates

    Great opportunity to work in true partnership with one of the UK's leading grocery retailing companies. This role is based within a premier supplie...

    • 21 days ago
  • Research Director - Research FMCG in Africa - Top Research

    London £55000-65000 per annum Resources Group

    This exciting opportunity focuses on the Africa region, a truly dynamic and changing consumer landscape which is growing at an exponential rate!

    • 7 days left
  • Quantitative Research Director | Ideation to strategy planning

    Melbourne AUD $120 to $150k plus SUPER Resources Group

    Insights, strategy and ideation. Give consumers a platform for open communication and work with brands to strategically respond to their needs.

    • 21 days ago
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To paraphrase Tennyson, in springtime, a man’s fancy turns to thoughts of landscaping. If you’ve got clients ready to start building or remodeling, you may be thinking not just about the inside of the house, but also about the outside. Chances are, many of your clients have their hearts set on a piece of rolling lawn, too, with fantasies of Downton Abbey dancing in their heads. But not so fast, says landscape designer Jonah Busick of Shepley Bulfinch Architects in Phoenix. Before you go ordering pallets of sod, Busick suggests telling your clients about the money they’ll save with xeriscaping.

Long associated with dry climates, prickly plants, and gravel paths, xeriscaping (also called xerogardening) isn’t just for the desert. It’s nothing more than smart landscaping that’s appropriate for the area you live in, says Busick. Yes, it originated in the West as a response to cutting back on water, but that mounting concern has since spread beyond arid places. "Something like 50% of domestic water is used for landscaping," says Busick.

Water shortages are only one reason to opt for this low-maintenance strategy, says Busick. You’ll use fewer pesticides and will save on lawn care bills, because plants that grow where they’re supposed to will stay healthier and need less babying. "The lawn used to be the default choice up until about 10 years ago," reports Busick. "But now people are thinking more critically."

Yet xeriscaping doesn’t have to mean foregoing that patch of green grass. "A lot of the landscaping we do is hybrid, where we do say 95% xeriscaping," he says. At the beginning of the design process, Busick asks clients exactly what they need a lawn for. If it’s for a dog or for kids to play outside—one of the main reasons people buy detached homes—he’ll often suggest a 10-foot by 20-foot patch of grass. In Phoenix, one variety he opts for is Bermuda grass, which doesn’t need much water.

There’s another reason to think about reclaiming the land and looking to the past when it comes to landscaping. Xero gardening, says Busick, beefs up property value. He advises that a well-considered landscape plan appropriate for its surroundings "helps organize design." "Tidy and appropriate translates to curb appeal," he says.

Amy Albert is a senior editor at Builder magazine.


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The Holiday Inn Crowne Plaza Jakarta is conveniently located in the busy golden triangle business district, surrounded by a myriad of offices, entertainment and commercial complexes. Reflecting the art deco period of the 20s with a casual design tone interior, Holiday Inn Crowne Plaza is a place where business and leisure go side by side.

  • Wifi
  • Restaurant Onsite
  • Pets Allowed
  • Property Size N/A
  • Conference Facility
  • Kids Allowed
  • Nearby City Jakarta
  • Nearby Water N/A
  • Open Dates All Year

Nearest Airports

  • Juanda International Airport (SUB) / 11.4 miles
  • Abdul Rachman Saleh Airport (MLG) / 48.7 miles
  • Trunojoyo Airport (SUP) / 80.3 miles

* Not all airports listed here may be open to public use, or service commercial flights

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Languages Spoken
  • English
Jakarta, Indonesia
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Spacious, Affordable Rooms on the Parkway in Pigeon Forge!

Be close to all of Pigeon Forge's best attractions and activities! Vacation Lodge offers guests comfortable, affordable accommodations and a location that is highly convenient. At Vacation Lodge you'll get much more than a place to sleep. The hotel also has great amenities like a heated outdoor pool, complimentary deluxe breakfast, and the trolley stops right in front of the building! Each guest room or mini-suite comes equipped with a microwave, refrigerator, coffee maker, and more. There are special accommodations for honeymooners and some rooms feature fireplaces and jacuzzis!

Pigeon Forge is a great destination for families! Vacation Lodge offers cozy accommodations that feature amenities such as flat screen LCD TV, microwave and more so you are sure to feel right at home. Spend your days touring the town and visiting attractions like Rainforest Adventures, Dixie Stampede, and Hoot 'n Holler.

If you're looking for great outdoor recreation, Pigeon Forge is not far from Great Smoky Mountain National Park. There you can enjoy the mountains in all their splendor. Hike or bike the many trails or explore the area's waterfalls. And when you're ready to relax, Vacation Lodge's cozy accommodations offer you a place to unwind after a day of fun.

Whether you're on your honeymoon or a spontaneous romantic escape to Pigeon Forge, the Honeymoon Suite at Vacation Lodge will provide you with an intimate place to enjoy each other's company. The suite has a jacuzzi, private balcony, and fireplace, everything you need for a comfortable getaway. When it comes to entertainment, Pigeon Forge offers plenty of fun places to visit from Dixie Stampede to the Great Smoky Mountains National Park.

  • Wifi
  • Restaurant Onsite
  • Pets Allowed
  • Property Size 93 units
  • Conference Facility
  • Kids Allowed
  • Nearby City Pigeon Forge
  • Nearby Water Little Pigeon River
  • Open Dates All Year

Plan your next group event at Vacation Lodge.

Pigeon Forge is a hub for family fun. If you're looking to host your next family reunion or group event in the area, the Vacation Lodge has accommodations to fit your needs!

For more information please call +1 (888) 328 - 7134 or Send Inquiry.

Nearest Airports

  • McGhee Tyson Airport (TYS) / 24.7 miles
  • Asheville Regional Airport (AVL) / 61.9 miles
  • Tri Cities Regional Tn Va Airport (TRI) / 79.8 miles

* Not all airports listed here may be open to public use, or service commercial flights

Additional Information

  • Swimming Pool
  • Mini Golf Course
  • Freshwater Fishing
  • Hiking
  • Wildlife & Nature
Room Amenities
  • Coffee Maker
  • Microwave
  • Go Carts
  • Horseback Riding
  • Live Entertainment
  • Shopping
  • Sightseeing
  • Swimming
  • Theme Parks
3450 Parkway Pigeon Forge, Tennessee 37863 United States
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This property is ranked number 2 on Top Pigeon Forge/Gatlinburg Hotels. Read about it here.


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Showing 1-15 of 23 Luxury Resorts

Random Haus

Palm Springs, California, United States

From the sleek, contemporary design, to the amazing amenities, you'll be surrounded by luxury during your stay at Random Haus! The hotel features 12 suites featuring plenty of space (1,100 to 2,100 square feet of impeccable sensory indulgence), large private patios and expansive decks. Flat-screen televisions, indoor and outdoor bars, Jacuzzi... more

  • Wifi
  • Restaurant Onsite
  • Pets Allowed
  • Property Size 12 units
  • Conference Facility
  • Kids Allowed
  • Nearby City Palm Springs
  • Nearby Water Diamond Valley Lake
  • Open Dates All Year
  • Nature
  • Romantic
  • Pet Friendly
  • Luxury
  • Mountain
  • Honeymoon

The Renovated Wyndham Palm Springs

Palm Springs, California, United States

A recent $5 million renovation has established Wyndham as the premier Palm Springs destination. Our elegant new lobby is a marriage of Spanish-colonial décor and California sunshine, with sweeping vistas of Palm Springs’ largest outdoor pool. The stunningly redesigned Café Terraza specializes in “California Fresh” cuisine, and the new... more

Sundance Villas

Palm Springs, California, United States

Your spacious villa near the Palm Springs Racquet Club is individually decorated in pure style. The kitchens are completely equipped, and each bedroom has its own bath. It's your private Palm Springs getaway with sunken tubs, central stereo, stone fireplaces and more.... more

Country Club and Resort Rentals

Palm Desert, California, United States

The spacious 42,000 square-foot, full service clubhouse features a very comfortable lounge and a dining room overlooking a huge lake, and offers a wonderful view of the surrounding mountains.... more

California Castle

Yucca Valley, California, United States

Palm Springs is synonymous with luxury and here you'll have the entire estate to yourselves, from the steam room and tanning beds to a pool area complete with waterfall and two Jacuzzis. The castle feature 3 kitchens, a tennis court and media room!... more

Estrella Inn

Palm Springs, California, United States

Sixty-seven luxury units give the choice of lavishly restored guest rooms, suites with private patios and balconies, and private bungalows with fireplaces.... more

Desert Falls Rentals

Rancho Mirage, California, United States

Outfitted for your perfect Palm Desert golf vacation, the luxury rentals of Desert Falls Rentals are set right at the fairways of beautiful Desert Falls or Portola Country Club.... more

Miracle Springs Resort and Spa

Desert Hot Springs, California, United States

Spend your next vacation at a resort that was featured in Vogue Magazine's "Elite Escapes.". Pamper yourself with great treatments at the spa, or soak your cares away in the waters of the natural hot springs. Then dine at the legendary Capri Italian Steakhouse and enjoy a libation in the lounge.... more

JW Marriott Desert Springs Resort & Spa

Palm Desert, California, United States
Very Good
1083 Reviews

An award-winning Lawn & Tennis Club and two championship golf courses are only the beginning of the luxurious amenities at JW Marriott Desert Springs. Ride through landscaped Venetian waterways, eat a gourmet meal and sleep in a lavishly adorned suite – all here, on your Palm Desert dream vacation.... more

Casa Cody

Palm Springs, California, United States

If you've come to relax, you've picked the right place! Casa Cody is a friendly, quiet country bed and breakfast inn featuring historic, luxury lodging in the prestigious tennis club area of Palm Springs, California.... more

Riviera Palm Springs Resort & Spa

Palm Springs, California, United States

The Riviera Resort & Spa features luxury that can only be achieved with time, taste, and a touch of legend. The new Riv is stunning in every detail, from the eclectic dining at Circa 59 to the signature treatments at SpaTerre. Your room will match your style - sophisticated and utterly comfortable.... more

Rancho Las Palmas Resort & Spa

Rancho Mirage, California, United States
Very Good
1011 Reviews

At Rancho Las Palmas you can truly indulge in a luxurious getaway unlike any you've experienced before. Discover a sanctuary at the Spa Las Palmas, excitement on the lush greens of a Ted Robinson designed course, and temptation at the delectable bluEmber restaurant.... more

Mojave Resort

Palm Desert, California, United States
Very Good
14 Reviews

From its palm-adorned courtyard to its luxury furnishings & amenities in each guest room or suite, Mojave Resort delivers luxury that's as modern as the outdoor pool and as timeless as the vintage video library - a true upscale Palm Desert vacation.... more

The Westin Mission Hills Resort & Spa

Rancho Mirage, California, United States
1484 Reviews

The Westin Mission Hills Resort & Spa offers a taste of true Palm Springs luxury. Indulge in a rejuvenating treatment at the Spa at Mission Hills, dine like a celebrity at Bella Vista, and enjoy golf on two championship courses. Your spacious accommodation also features thoughtful amenities and beautiful Palm Springs views.... more

Tahquitz Creek

Palm Springs, California, United States

Tahquitz Creek Golf Resort offers a full range of amenities which include: 150 stall grass driving range, chipping green, two large putting greens, PGA/LPGA golf instruction, and can accommodate your tournament, corporate function, banquet or friendly group outing needs. ... more

Showing 1-15 of 23 Luxury Resorts

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Southern Minnesota Articles

Showing 1-3 of 3 Ski Resorts

Eagles on the River Vacation Rentals

Wabasha, Minnesota, United States

Head to Eagles on the River Vacation Rentals in the winter months and enjoy some great skiing! Boasting the steepest vertical drop in all of southern Minnesota, both experts and beginners alike will enjoy the wintery slopes. Just one more reason to book your vacation at Eagles on the River today!... more

  • Wifi
  • Restaurant Onsite
  • Pets Allowed
  • Property Size N/A
  • Conference Facility
  • Kids Allowed
  • Nearby City Wabasha
  • Nearby Water Mississippi River
  • Open Dates All Year
  • Family
  • Golf
  • Nature
  • Fishing
  • Romantic
  • Ski/Snowboard
  • Pet Friendly
  • Historical
  • Cabins, Cottages, and Chalets

Smitty's On Snowbank

Le Sueur, Minnesota, United States

Glide through silent forests on fresh, deep powder. Smitty’s On Snowbank is an official access point to the BWCA and situated less than five miles from the Canadian border.... more

Wise-Stop Resort

Greenland, Minnesota, United States

Spend a day on the slopes! Nearby Mount Kato offers excellent downhill skiing, with a wide variety of trails to appeal to beginner and expert alike.... more

Showing 1-3 of 3 Ski Resorts

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3-, 4-, and 5-Bedroom Multi-Level Townhomes Within Yards from the Slopes

Boasting a location that provides a year-round mountain retreat setting and large luxury townhomes bustling with amenities, Waterstone at EagleRidge is a great choice for a vacation to Steamboat Springs in Colorado. Winter visitors will love Waterstone’s location just 300 yards from the gondola and world-class skiing. Summer vacationers will find the location along the winding Burgess Creek enticing for outdoor adventure. With its inventory of multi-level and spacious 3-, 4- and 5-bedroom townhomes featuring washer/dryers, gourmet kitchens, fireplaces and a jetted tub in the master, this lodge is great for groups of varying sizes. Guests can take advantage of a shuttle service in the winter to find shopping, dining and entertainment. With its mountainous terrain and snow-filled winters, the EagleRidge area offers world-class skiing and winter activities fit for the entire family and people of all ages and skill levels. Nestled peacefully along the picturesque Burgess Creek and trail, visitors during the warmer months can enjoy great hiking, biking, fishing, water sports and other outdoor activities that showcase the natural beauty of this location.

Town Home

  • Bedrooms 5
  • Bathrooms 5
  • Sleeps 12
  • Nearby City Boulder
  • Nearby Water N/A
  • Open Dates All Year

Nearest Airports

  • Eagle County Regional Airport (EGE) / 56.4 miles
  • Aspen-Pitkin Co/Sardy Field (ASE) / 85.1 miles
  • Laramie Regional Airport (LAR) / 83.8 miles

* Not all airports listed here may be open to public use, or service commercial flights

1463 Flattop Circle Steamboat Springs, Colorado 80487 United States
Phone Number

+1 (970) 879 - 8000

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Thread: Dogs watching TV

  1. #1
    Senior Member Fowl Play WA's Avatar
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    NW Washington

    Default Dogs watching TV

    My daughter was watching "It's Me or the Dog" this morning sitting in her beanbag chair in front of the couch. Gunner, the blm was sitting in my husband's lap, watching also. After all it was a show about two unruly labs. Harleigh stood up and Gunner couldn't see so he stood up on the couch, moved to the other side, and leaned around her so he could continue watching.

    Before Victoria, they had "K 9-5" and the dog job they were featuring was this obese lab that worked on a construction site. Gunner walked up to the TV and smashed his nose into it and followed the dog across the roof of the house (leaving a beautiful nose smear across the TV) and when the dog was out of the picture he barked at it.

    I think I've allowed him to watch too much TV. He gets mad at the kid when she plays door.

    **On a side note...just a minute observation about the "American vs British" lab controversy. Whenever Victoria Stillwell goes to a home in England with a lab, they are conveniently a thin "American" style. Kind of squashes that theory a bit unless they're saying that "American" labs are crazy on that side of the pond too.
    I don't wear black because it makes me look slim, I wear black because it hides the dog hair.

  2. #2
    Senior Member Don Smith's Avatar
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    Mar 2004
    New Albany, OH

    Mine occasionally watch TV, especially Waterdog TV and DU TV. What threw me for a loop today was, while watching a DVD I just got on WWII, little Lilly seemed to be especially interested in and interview Traudl Junge, Hitler's personal secretary. Go figure. LOL
    HRCH Meglyn's Maramaxx Daisycutter MH (Daisy)
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    Meglyn's Lionheart MH (Little Guy)
    Meglyn-Firemark's I am NOT a Lab SH (Goldie)
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    In memory of Chevy, HR Meglyn's Silverado Slim SH, July 20, 2006, HR Meglyn's Blue Ridge Belle MH, July 19, 2008 and HRCH Meglyn's Honest Abe MH, Aug 9, 2014.

  3. #3
    Senior Member windycanyon's Avatar
    Join Date
    Dec 2007
    WA State

    My old granny girl still loves commercials esp with dogs on them. I have an old big screen TV that she's scratched (offering nylabones to the dogs on the screen) over the years. At 13.5, she still flies off the couch to go greet them w/a woof.

    Yesterday there was a duck hunting show on network TV and the youngsters who don't seem nearly as interested normally all jumped up and marked the ducks as they were being shot! Anne

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Thread: Umbrella Stand

  1. #1
    Senior Member jeff t.'s Avatar
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    North Carolina

    Default Umbrella Stand

    II need an umbrella stand...I've seen the one that Lion Country Suppy sells, are there others that you recommend?
    Jeff Telander
    Durham, NC

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    The only ones that I have personally seen are the ones from LCS. They are really nice and everyone I know that owns one just loves it.

    "You can't win until you are not afraid to lose."

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    What Andy said!

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About a week ago, I wrote a list article that showed my 5 favorite films of the 90s that left folks with mixed feelings. Some thought I had made terrible choices, others thought I made the right choices. So, to quiet those who whined about my first list article, I created another list of 90s movies that are definitely classics.

5. Terminator 2: Judgment Day (1991) - This was an action-packed saga of the near-future that brilliantly balances a well-told story and cutting-edge visual effects without the effects overpowering the story. One of the great sci-fi/action movies of the decade.

4. Braveheart (1995) - A story of William Wallace's epic fight for freedom for his people, Mel Gibson directs & stars in this drama that is often brutal yet hopeful with some of the best battle sequences captured on film. Once you see it, you can see why it deserved so many awards.

3. Fight Club (1999) - It's hard to explain what the movie is about (I'm speaking from viewing experience) but what you need know about the 3rd directorial effort of David Fincher is it's secret underground fight clubs, airplane disasters & eccentric personalities. Not to mention the great performances of Brad Pitt & Ed Norton.

2. Forrest Gump (1994) - After seeing this in 1994, I was beginning to be interested in some of the true historical events that the title character has encountered over the years. The way Tom Hanks acted in this film & the way Robert Zemeckis directed it, it can't be topped, not even today.

1. Pulp Fiction (1994) - I had to wait until 2002 to see this spectacular ensemble caper and when I did, the film blew me away. Everything about this was awesome, from the cast to the screenplay to the music. Not only is it a 90s classic, I credited this, along with others, for inspiring to pursuit a career in filmmaking.

These films are entertaining, great to watch & it helps you realize that these movies defined a decade, a generation. You look at them today and they're not even close to being dated. That's how good they are.


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Can you use a visa or MasterCard gift card to buy this game?
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yes you can, you do it through paypal, you do not need a paypal account, you can go into paypal and be a 'paypal guest' which is basicly your just using your credit card through paypal without actually having a paypal account.

We hope to have more pay options in the near future.
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“Somewhat satisfactory”

Written on: 20/11/2012

Service was good. They quoted me a good price, told when my clubs would be delivered and then delivered them as promised. However, I doubt the item was genuine one… Read Full Review

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thinks he's in hollywood.

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BorisStanway's review of

“thinks he's in hollywood.”

Written on: 04/02/2014 by BorisStanway (0 reviews written)

In an ideal world, "mike" would press the record button, and then leave the room.

He doesn't do this, partly because the way he treats some younger "aspiring" models is often questionable (he needs to be able to handle them -- this subject might not be for this review), partly because his filming is about his portfolio.

mike needs to sell his camera, and buy one which has only one button - "record".

He then needs to put the camera on a tripod, because most of his productions look like he was on the whisky at the time. Circling around the room like a helicopter and being out of focus for half of the filming, is not artistic. it's rubbish.

It's possible the poses are just something he's decided to buy into. A lot of his filming concentrates on walking around the room and zooming. there ain't much point in filming someone doing something, if all you can see is their ear or nose or elbow. His standards for his productions seem to be based upon his own self defined 'reputation'. And since it's relatively niche, it rarely gets challenged.

A bloke and a camera. And some other stuff that happens to be in the room. That explains his film reels. It's "look at me", and filming something. This wouldnt be quite so bad, if he wasn't anti competitive about other people who are actually doing a decent job.

That's the sign of bad quality. You attack others material. he has a niche, so he has the power to harass other people in the industry. mike como is a case of vhs over betamax. That's why he's so protective of it. The mark of classic sub standard "if you think you can do better".

People have sent him their own home productions before. mike manages to ruin these as well, by being a 12 year old who can't stop pressing buttons on the editing suite. He has his production logo constantly in the video. Sure, this gets in the way. But more importantly, people must know his branding.

When Peter Jackson was filming lord of the rings, he opted for a RED one. mike has gone for a "sellotape a camera on some string underneath a fly" look. I don't know if this is the industry or just this particular bloke, but mike definitely has a "dont give a #### impression of what he's filming.

His aim seems to be that someone else will see his videos, and go "wow, this guy is so good at filming, lets get him to film our vids". He can then set up some more paypal sites. Fly mounted camera's dont come cheap, y'know.

A case of reputation based upon suppressing criticism. There seem to be two types of business. One where you take onboard criticism and improve your product accordingly, and one where you fling #### in your desired location.

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“Great shopping experience ”

Written on: 15/08/2012

I ordered a Charge 'Spoon' saddle on Sunday night from Triton Cycles, at an excellent price; the cheapest on the Internet.
It arrived first thing on Tuesday and that was with free delivery! It was an excellent shopping experience and I will certainly check them out next time I'm buying stuff. I can also report that the Charge 'Spoon' saddle is really excellent value for money and is one of the best fitting saddles (for me) that I have even ridden on.