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Mechlin C.W.,Albany Medical College | Tanner M.J.,The Ordway Research Institute Inc. | Chen M.,The Ordway Research Institute Inc. | Buttyan R.,Albany Medical College | And 5 more authors.
Journal of Urology | Year: 2010

Purpose: Hedgehog signaling regulates Gli transcription factors. Aberrant hedgehog signaling can be oncogenic and drugs that block hedgehog are being tested as anticancer agents. We considered whether hedgehog/Gli signaling may be involved in human bladder transitional cell carcinoma proliferative or invasive behavior. Materials and Methods: We stratified the human bladder transitional cell carcinoma lines RT4 (ATCC®), 253JP, 253BV, UMUC6 and UMUC3 for relative growth rate by cell counting and for in vitro invasiveness by Matrigel™ invasion assay. Cells were tested for growth inhibition by the hedgehog blocking drug cyclopamine or the inactive mimic tomatidine. Cell RNA was characterized for hedgehog signaling component expression, including ligands, receptors and signaling mediators, by quantitative reverse transcriptase-polymerase chain reaction. Gli2 expression or activity was modified by Gli2 expression lentiviruses or the Gli inhibitor GANT61. We measured effects on proliferation and invasiveness. Results: Cell growth rates and invasiveness were stratified into an equivalent order (RT4 <243JP <253BV

Phelps K.R.,Stratton Veterans Affairs Medical Center | Lieberman R.L.,Albany Medical College
Clinical Nephrology | Year: 2012

The concepts of fractional excretion and reabsorption are often employed to elucidate the contribution of tubular transport to plasma concentrations. Fractional excretion of substance x, FEx, is the ratio of the urinary excretion rate to the filtration rate of x, or Ex/Fx. Fractional tubular reabsorption of x, FTRx, is the ratio of the reabsorption rate to the filtration rate of x, or TRx/Fx. When plasma is in equilibrium with respect to x, net influx (Ix) from gut and tissue determines Ex, and [x]p = Ex/GFR + TRx/GFR. In chronic kidney disease (CKD), Ex/GFR rises as GFR falls if Ix does not fall commensurately; at the same time, TRx/GFR may fall, remain unchanged, or rise. If TRx/GFR rises, a simultaneous, proportionately greater increment in Ex/GFR causes FEx to rise also and FTRx to fall secondarily. In this circumstance, FTRx is lower than normal even though reabsorption of x is increased per volume of filtrate. This paper reviews pertinent homeostatic principles, illustrates the potential for divergence of TRx/GFR and FTRx as GFR falls, and summarizes the conditions required for the divergence. Clinical examples show reduced FTRx despite increased TRx/GFR for phosphorus and urate, and analyses suggest that such discrepancies are often inevitable. Methods are described and arguments are advanced for using TRx/GFR to quantify tubular function in CKD. © 2012 Dustri-Verlag Dr. K. Feistle.

Phelps K.R.,Stratton Veterans Affairs Medical Center | Phelps K.R.,Albany Medical College | Stote K.S.,Albany State University | Mason D.,Albany Medical College | Mason D.,Albany College of Pharmacy and Health Sciences
Clinical Nephrology | Year: 2014

Aims: Parathyroid hormone (PTH) promotes calcium reabsorption in the cortical distal nephron (CDN). The phosphate concentration ([P]f) rises in that segment in chronic kidney disease (CKD); in theory, high [P]f could reduce availability of calcium for reabsorption and necessitate a compensatory rise in [PTH]. With assumptions, [P]f is proportional to phosphate excreted/volume of filtrate (EP/GFR). We therefore hypothesized that [PTH] would correlate with EP/GFR in CKD, and δ[PTH] would correlate with δEP/GFR after sevelamer therapy. Methods: We conducted a 4-week, placebo-controlled trial of sevelamer carbonate in patients with CKD. [PTH]1-84 and parameters of phosphate homeostasis were measured before and after treatment. GFR was assumed to equal creatinine clearance (Ccr). Pertinent linear regressions were performed. Results: Phosphate excretion fell in the sevelamer group only. Decrements in [PTH] with sevelamer differed from increments with placebo. With either treatment, [PTH] correlated with EP/Ccr and δ[PTH] correlated with δEP/Ccr. Changes in [PTH] were minimal in some sevelamer recipients despite reductions in EP/Ccr; calcium excreted/volume of filtrate was low in these subjects. Conclusions: Phosphate influx affected [PTH] in CKD by determining [P]f in the CDN. In some patients, low calcium influx may have blunted the effect of sevelamer on [PTH]. © 2014 Dustri-Verlag Dr. K. Feistle.

Mahrer A.,Stratton Veterans Affairs Medical Center | Ramchandani P.,University of Pennsylvania | Trerotola S.O.,University of Pennsylvania | Shlansky-Goldberg R.D.,University of Pennsylvania | Itkin M.,University of Pennsylvania
Journal of Vascular and Interventional Radiology | Year: 2010

Purpose: To describe a single-center experience with sclerotherapy of postoperative lymphocele and to determine the risk factors for failure of treatment. Materials and Methods: From 1999 to 2007, 43 patients with postsurgical lymphocele were treated with sclerotherapy with a combination of povidone iodine, alcohol, and doxycycline. The treatments were repeated at weekly intervals. The initial drainage volume of the lymphocele, the location of the lymphocele, the number of treatments, and the outcomes were retrospectively collected. Results: In 38 patients, the lymphocele was drained percutaneously, and in five patients, the treatment was initiated through an existing surgically placed drainage tube. Sclerotherapy was successful in 33 patients (77%). Complications that resulted in termination of the treatment were seen in five patients (12%): testicular pain, cellulitis, posttreatment increase in creatinine, acute renal tubular necrosis, and abdominal infection. In one of these patients the lymphocele resolved after resolution of the infection. The average number of treatments was four (range, 1-14). There was no difference in success rate between superficial intraabdominal and soft-tissue lymphoceles. There was a significant difference (P < .05) in the fluid volume at initial drainage between the failure group (1,708 mL ± 1,521) and the success group (206 mL ± 213). This assumes an attempt was made to drain the collection completely at the initial procedure. Conclusions: Sclerotherapy of postoperative lymphoceles is an effective treatment. Success of sclerotherapy is directly related to the size of the lymphocele cavity. © 2010 SIR.

Atkinson T.J.,Stratton Veterans Affairs Medical Center | Fudin J.,Stratton Veterans Affairs Medical Center | Fudin J.,The Academy of Management | Fudin J.,Albany College of Pharmacy and Health Sciences | And 5 more authors.
Pain Medicine (United States) | Year: 2013

Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) represent a critically important class of medications useful in numerous musculoskeletal and inflammatory diseases. The focus of NSAID use has recently centered on gastrointestinal (GI) side effects and potential cardiovascular toxicity. Innovative new oral and intra-articular pharmaceutically engineered dosage forms are examined. We review recently developed intravenous NSAIDs and their potential advantages over oral products in the perioperative setting. Design: Databases searched included PubMed, Google Scholar, Ovid, and Athens. We contacted key U.S. and Japanese manufactures who are developing new and innovative NSAID technologies for inclusion in this overview. Early attempts at mitigating GI toxicity with oral agents combined with gastroprotective additives are outlined. Results: Contemporary technologies coupled with uniquely advanced pharmaceutical manipulations to improve safety and efficacy are discussed including combined vasodilating agent naproxcinod as the prototypical cyclooxygenase-inhibiting nitric oxide (NO) donor; hydrogen sulfide-releasing compounds to protect GI mucosa; glycoscience technologies combining the intra-articular hyaluronic acid SI-613 combined with NSAIDs; and nano-formulated SoluMatrix submicron technologies that include diclofenac, indomethacin, naproxen, and meloxicam. Conclusions: New NSAIDs under development are intended to address GI and cardiovascular pitfalls inherent to current therapy options across the entire NSAID drug class. NO or hydrogen sulfide donating drugs, new reliable injectables for perioperative and inpatient use, novel intra-articular extended-release NSAIDs combined with IAHA, and nano-formulations of submicron NSAIDs featuring delivery of decreased doses without diminished efficacy promise to afford innovative technologies that likely will be the future of NSAID therapy. © 2013 Wiley Periodicals, Inc.

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