Kansas City, MO, United States
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Gutheil W.G.,University of Missouri - Kansas City | Reed G.,University of Kansas | Ray A.,University of Minnesota | Anant S.,University of Kansas | And 2 more authors.
Current Pharmaceutical Biotechnology | Year: 2012

Cancer is one of the leading causes of death in the United States and accounts for approximately 8 million deaths per year worldwide. Although there is an increasing number of therapeutic options available for patients with cancer, their efficacy is time-limited and non-curative. Approximately 50-60% of cancer patients in the United States utilize agents derived from different parts of plants or nutrients (complementary and alternative medicine), exclusively or concurrently with traditional therapeutic regime such as chemotherapy and/or radiation therapy. The need for new drugs has prompted studies evaluating possible anti-cancer agents in fruits, vegetables, herbs and spices. Saffron, a spice and a food colorant present in the dry stigmas of the plant Crocus sativus L., has been used as an herbal remedy for various ailments including cancer by the ancient Arabian, Indian and Chinese cultures. Crocetin, an important carotenoid constituent of saffron, has shown significant potential as an anti-tumor agent in animal models and cell culture systems. Crocetin affects the growth of cancer cells by inhibiting nucleic acid synthesis, enhancing anti-oxidative system, inducing apoptosis and hindering growth factor signaling pathways. This review discusses the studies on cancer preventive potential of crocetin and its future use as an anticancer agent. © 2012 Bentham Science Publishers.


Rao G.A.,Kansas City Veterans Affairs Medical Center | Rao G.A.,University of South Carolina | Pandya P.K.,Kansas City Veterans Affairs Medical Center | Pandya P.K.,University of Kansas
Gastroenterology | Year: 2011

Background & Aims: Patients with chronic hepatitis C infection are 2- to 3-fold more likely to develop type 2 diabetes, which reduces their chances of achieving a sustained virologic response (SVR). To identify differences in predictors of SVR in patients with and without diabetes who received combination antiviral therapy, we conducted a retrospective analysis of a national Veterans Affairs administrative database. Methods: We analyzed data from the Veterans Affairs Medical SAS Datasets and Decision Support System for entire cohort and separately for diabetic patients (n = 1704) and nondiabetic patients (n = 6589). Significant predictors of SVR were identified by logistic regression analysis. Results: Diabetic patients had a lower SVR compared with nondiabetic patients (21% vs 27%, respectively, P < .001). Diabetic patients had higher clustering of previously established negative predictors of SVR. On multivariate analysis of diabetic patients for SVR, the positive predictors were higher low-density lipoprotein (odds ratio [OR], 1.45; P = .0129), use of statin (OR, 1.52; P = .0124), and lower baseline viral load (OR, 2.31; P < .001), whereas insulin therapy (OR, 0.7; P = .0278) was a negative predictor. Diabetic patients on statins had higher pretreatment viral loads (log 6.2 vs 6.4, respectively, P = .006) but better early virologic response. There was a graded inverse relationship between Hemoglobin A1c and SVR rate (P = .0482). This relationship was significant among insulin users (P = .0154) and non-significant among metformin users (P = .5853). Conclusions:: Statin use was associated with an improved SVR among both diabetic patients and nondiabetic patients receiving combination antiviral therapy. Diabetic patients who received insulin achieved lower SVR compared with those not receiving insulin. Poor diabetes control was associated with lower SVR rates. © 2011 AGA Institute.


Campbell A.R.,Center for Behavioral Medicine | Anderson K.D.,Kansas City Veterans Affairs Medical Center
American Journal of Health-System Pharmacy | Year: 2010

Purpose. The effects of varenicline treatment for smoking cessation on mental health (MH) stability in veterans with posttraumatic stress disorder (PTSD) was studied. Methods. Data were collected by retrospective chart review at a Veterans Affairs medical center. Patients with PTSD who were prescribed varenicline for smoking cessation between May 2006 and July 2008 were included; all patients had failed previous attempts to quit using nicotine replacement therapy, bupropion, or both. The average numbers of encounters per month with MH professionals in a six-month baseline period before varenicline, during treatment, and after treatment were compared. The numbers of MH encounters were compared for patients with multiple MH disorders including major depressive disorder, schizophrenia, or bipolar disorder and those with PTSD alone. Patients who had completed a full course of varenicline therapy (4-12 weeks) without MH decompensation were surveyed to determine the rate of smoking cessation. Results. Data were analyzed for 78 patients. MH encounters during varenicline therapy increased 29% over baseline. There was no significant difference in the numbers of encounters in the baseline and postvarenicline periods. MH decompensations were documented for 4 patients during varenicline therapy and 2 after completion of therapy. Before, during, and after varenicline, patients with multiple MH disorders had significantly more MH encounters than those with PTSD alone. Of the 42 patients in the follow-up survey, 19 (45%) said they refrained from smoking for 30 days and 13 (31%) for 90 days. Conclusion. Varenicline appeared to have destabilizing effects on MH in veterans with PTSD.


Madhoun M.F.,The University of Oklahoma Health Sciences Center | Wani S.B.,Aurora University | Rastogi A.,Kansas City Veterans Affairs Medical Center | Early D.,University of Washington | And 3 more authors.
Endoscopy | Year: 2013

Background and study aims: It is uncertain if needle gauge impacts the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic mass lesions. Our aim was to use meta-analysis to more robustly define the diagnostic accuracy of EUS-FNA for pancreatic masses using 22 G and 25 G needles. Patients and methods: Studies were identified by searching nine medical databases for reports published between 1994 and 2011, using a reproducible search strategy comprised of relevant terms. Only studies comparing the overall diagnostic accuracy of 22 G vs. 25 G EUS needles that used surgical histology or at least 6 months clinical follow up for a gold standard were included. Two reviewers independently scored the identified studies for methodology and abstracted pertinent data. When required, the original investigators were contacted to provide additional data. Pooling was conducted by both fixed-effects and random-effects models. Diagnostic characteristics (sensitivity, specificity, positive and negative likelihood ratios) with 95 % confidence intervals (CIs) were calculated. Results: Eight studies involving 1292 subjects met the defined inclusion criteria. Of the 1292 patients, 799 were in the 22 G group and 565 were in the 25 G group (both needles were used in 72 patients). The pooled sensitivity and specificity of the 22 G needle were 0.85 (95 %CI 0.82 - 0.88) and 1 (95 %CI 0.98 - 1) respectively. The pooled sensitivity and specificity of the 25 G needle were 0.93 (95 %CI 0.91 - 0.96) and 0.97 (95 %CI 0.93 - 0.99) respectively. The bivariate generalized linear random-effect model indicated that the 25 G needle is associated with a higher sensitivity (P = 0.0003) but comparable specificity (P = 0.97) to the 22 G needle. Conclusions: This meta-analysis suggests 25 G needle systems are more sensitive than 22 G needles for diagnosing pancreatic malignancy.© Georg Thieme Verlag KGStuttgart . New York.


Dhar A.,Kansas City Veterans Affairs Medical Center | Dhar A.,University of Kansas | Ray A.,Kansas City Veterans Affairs Medical Center
Experimental Oncology | Year: 2010

The CCN (Cyr61 (cysteine-rich protein 61), CTGF (connective tissue growth factor), Nov (nephroblastoma overexpressed)) fami ly consists of six members that belong to matricellular proteins of extracellular matrix (ECM). Like other matricellular proteins, CCN members do not primarily have a structural role; however, they modulate cell-ECM interactions. In general, CCN proteins are formed by four characteristic domain structures and thought to participate in various biological phenomena such as organ development, wound healing, angiogenesis, fibrosis, etc. In cancer, CCN proteins family expresses aberrantly; probably depending on the sites and types, expressions of different CCN proteins have been documented to be linked with either progression or inhibition of the pathological processes of cancer. Through various mechanisms like cell survival, apoptosis, inflammation, cell adhesion and migration and connection with several cytokines, CCN proteins perhaps influence the disease course including tumor metastasis. A majority of the above-mentioned effects are believed to be mediated by binding with integrins, a class of receptors that mediate cell-cell and cell-ECM interactions. Furthermore, the members of CCN family modulate the functions of several important growth factors and related pathways such as insulin-like growth factor (IGF), transforming growth factor-β (TGF-β) and Wnt signaling. Interestingly, a variety of factors/proteins linked with these signaling systems are reported to be associated with the carcinogenic process. Nevertheless, a precise knowledge about the pathophysiological activities including signaling pathways of CCN proteins would be helpful to identify molecular targets in order to design therapeutic strategies in the management of cancer. Copyright © Experimenta Oncology, 2010.


Kanakadandi V.,Kansas City Veterans Affairs Medical Center | Sharma P.,Kansas City Veterans Affairs Medical Center | Sharma P.,University of Kansas
Gastrointestinal Endoscopy: New Technologies and Changing Paradigms | Year: 2015

Barrett’s esophagus (BE) is the replacement of stratified squamous epithelium of the distal esophageal mucosa with columnar epithelium with intestinal metaplasia. It is the only known premalignant condition that predisposes to the development of esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has increased several folds over the last few years, and it is associated with a poor prognosis when diagnosed late. Endoscopic screening and surveillance of patients with BE is done to detect the progression to cancer and to treat it at an early stage. BE is diagnosed by endoscopy and biopsy. The standard endoscopic procedures include noting the circumferential and maximal extent of BE, characterization of visible lesions by Paris classification and rigorous four-quadrant random biopsy. Advanced imaging techniques, such as chromoendoscopy, auto-fluorescence imaging, narrow-band imaging, optical-coherence tomography and confocal endomicroscopy, aid in the diagnosis of dysplasia. BE progresses through stages of non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and esophageal adenocarcinoma (EAC). The risk of cancer progressively increases through each of the stages of dysplasia and is 6.6% in patients with HGD. Patients with HGD are, therefore, treated with endoscopic therapies to reduce the risk of their progression to cancer. A number of endoscopic techniques are available for the eradication of dysplasia; multi-polar electrocoagulation, argon plasma coagulation, photodynamic therapy, cryotherapy, radiofrequency ablation (RFA), and endoscopic mucosal resection (EMR). EMR of visible lesions and RFA of remaining BE is the current standard practice and results in eradication of >90% of BE epithelium. Strictures are the most common complication and are seen in 5% of the patients undergoing RFA. Recurrence is seen in one fourth of the patients and underscores the need for continued surveillance even after the treatment. Long-term efficacy studies are needed to assess the impact of endoscopic eradication. In the future, peptide-based imaging, Raman spectroscopy, biomarker panels, and genomic sequencing will be used in managing these patients. © Springer Science+Business Media New York 2015.


Timberlake G.T.,Kansas City Veterans Affairs Medical Center | Timberlake G.T.,University of Kansas Medical Center | Omoscharka E.,Kansas City Veterans Affairs Medical Center | Quaney B.M.,Kansas City Veterans Affairs Medical Center | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2011

PURPOSE. Vision plays a critical role in reaching and grasping objects. Consequently, bilateral macular scotomas from agerelated macular degeneration (AMD) may affect reach-to-grasp movements. The purpose of this work was to investigate changes in reach-to-grasp movement dynamics and to relate those changes to the characteristics of subjects' preferred retinal loci (PRL), scotomas, and visual acuities. METHODS. Three-dimensional positions of the index finger and thumb were recorded while subjects with bilateral scotomas and subjects with normal vision reached for and grasped blocks of three widths at two distances under binocular and monocular viewing conditions. Reach-dynamic parameters and the grip aperture (thumb-index finger distance) were calculated. Retinal locations and sizes of subjects' scotomas and PRLs were mapped with a scanning laser ophthalmoscope. RESULTS. Scotoma subjects' hand trajectories had longer movement durations, lower maximum velocities, and longer visual reaction times than those of control subjects. With monocular viewing, maximum grip aperture (MGA) increased as a function of block width at a significantly higher rate for scotoma subjects than for control subjects. MGA decreased with increasing PRL bivariate normal ellipse area, and visual reaction time increased with decreasing acuity of the eye tested. CONCLUSIONS. Compared with normally sighted subjects, subjects with bilateral macular scotomas from AMD have reach-tograsp movements with longer trajectories, longer visual reaction times, lower velocities, and altered MGA-block width scaling. Visual reaction time and MGA are directly related to PRL characteristics. Deficits in reach-to-grasp movement caused by macular scotomas are greater in degree than those reported by others for real or artificial peripheral scotomas. © 2011 The Association for Research in Vision and Ophthalmology, Inc.


Oni O.,Kansas City Veterans Affairs Medical Center
American journal of disaster medicine | Year: 2012

Experiencing natural disasters such as hurricanes is associated with post-traumatic stress disorder (PTSD) and depression. We examined the role played by perceived stress and coping styles in explaining and modifying this association among pregnant women exposed to Hurricane Katrina. The study comprised 192 women (133 from New Orleans and 59 from Baton Rouge) who were pregnant during Hurricane Katrina or became pregnant immediately after the hurricane. Women were interviewed regarding their hurricane experience, perceived stress, and mental health outcomes. Coping styles was assessed using the Brief COPE, PTSD symptoms using the Post-Traumatic Checklist, and depressive symptoms using the Edinburgh Depression Scale. Multivariable regression models were run to determine the effects of coping styles on mental health and the interactions among coping styles, hurricane experience, and perceived stress on mental health. Apart from the positive reframing and humor coping styles, all coping styles correlated positively with PTSD or depression (p < 0.05). The instrumental support, denial, venting, and behavioral disengagement coping styles were significantly associated with worsened PTSD symptoms among those who reported higher perceived stress (p < 0.05). Use of a humor coping style seemed to reduce the effect of perceived stress on depressive symptoms (p = 0.02 for interaction) while use of instrumental support (p = 0.04) and behavioral disengagement (p < 0.01) were both associated with more symptoms of depression among those who perceived more stress. There were no strong interactions between coping style and hurricane experience. Coping styles are potential moderators of the effects of stress on mental health of pregnant women.


Timberlake G.T.,Kansas City Veterans Affairs Medical Center
Investigative ophthalmology & visual science | Year: 2012

Fine manual tasks require coordination of vision, eye movements, and motor control. Macular scotomas from age-related macular degeneration (AMD) may adversely affect this coordination. The purpose of this research was to find whether the preferred retina locus for fixation (fPRL) also guided the hand in performing fine manual tasks and how the fingers, fPRL, and scotomas interacted in task performance. Subjects with bilateral macular scotomas from AMD and normally sighted controls traced an irregular "maze" line pattern with the index finger while viewing their hand and the maze in a scanning laser ophthalmoscope (SLO). Video images from the SLO showing the fingers and maze on the retina during the task were analyzed to produce retinal maps showing the scotoma and bivariate ellipses of fPRL and fingertip retinal positions. Fingertip retinal ellipses surrounded and were approximately centered on the fPRL ellipses. Fingertip retinal bivariate area was positively correlated with fPRL bivariate area and the percent time the fPRL was on the maze was correlated with visual acuity. Maze-tracing accuracy was positively correlated with saccade rate for scotoma subjects. Concentric overlap of fPRL and fingertip retinal ellipses indicates that it is the fPRL that guides the hand in the maze-tracing visuomotor task, just as the fovea guides the fingertip for visually normal subjects. It is likely that factors other than fPRL and scotoma characteristics contribute to poorer maze-tracing performance by scotoma subjects in comparison with controls.


Gupta N.,Kansas City Veterans Affairs Medical Center | Gupta N.,University of Kansas Medical Center | Gaddam S.,Kansas City Veterans Affairs Medical Center | Wani S.B.,Kansas City Veterans Affairs Medical Center | And 7 more authors.
Gastrointestinal Endoscopy | Year: 2012

Current guidelines recommend that endoscopic surveillance of Barrett's esophagus (BE) be performed by using a strict biopsy protocol. However, novel methods to improve BE surveillance are still needed. To evaluate the impact of Barrett's inspection time (BIT) on yield of surveillance. Post hoc analysis of data obtained from a clinical trial. Five tertiary referral centers. Patients undergoing BE surveillance. Coordinators prospectively recorded the time spent inspecting the BE mucosa with a stopwatch. Endoscopically suspicious lesions, high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC). A total of 112 patients underwent endoscopic surveillance by 11 individual endoscopists. Patients with longer BITs were more likely to have an endoscopically suspicious lesion (P < .001) and more endoscopically suspicious lesions (P = .0001) and receive a diagnosis of HGD/EAC (P = .001). There was a direct correlation between the endoscopist's mean BIT per centimeter of BE and the detection of patients with HGD/EAC (ρ = .63, P = .03). Endoscopists who had an average BIT longer than 1 minute per centimeter of BE detected more patients with endoscopically suspicious lesions (54.2% vs 13.3%, P = .04), and there was a trend toward a higher detection rate of HGD/EAC (40.2% vs 6.7%, P = .06). Post hoc analysis of an enriched study population and experienced endoscopists at tertiary referral centers. Longer time spent inspecting the BE segment is associated with the increased detection of HGD/EAC. Taking additional time to perform a thorough examination of the BE mucosa may serve as an easy and widely available method to improve the yield of BE surveillance. © 2012 American Society for Gastrointestinal Endoscopy.

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