Griffith B.P.,University of Maryland, Baltimore |
Anderson M.B.,Johnson University |
Samuels L.E.,Lankenau Medical Science Hospital |
Pae Jr. W.E.,Penn State Hershey Heart and Vascular Institute |
And 2 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2013
Objectives: Cardiogenic shock after cardiac surgery is accompanied by a high mortality rate. Early institution of hemodynamic support with a versatile, easy to insert left ventricular assist device might help bridge patients to recovery or to the next therapy, and improve the outcomes. Methods: Patients developing cardiogenic shock or low cardiac output syndrome after being weaned off cardiopulmonary bypass were enrolled in a prospective single-arm feasibility study (RECOVER I). The primary safety endpoint was the frequency of major adverse events (death, stroke) at 30 days or discharge, whichever was longer. The primary efficacy endpoint was survival of the patient to implementation of the next therapy, which included recovery at 30 days after device removal and bridge-to-other-therapy. Results: Sixteen patients provided informed consent and were enrolled in the study. Hemodynamics improved immediately after the initiation of mechanical support: cardiac index, 1.65 versus 2.7 L/min/m 2 (P = .0001); mean arterial pressure, 71.4 versus 83.1 mm Hg (P = .01); and pulmonary artery diastolic pressure, 28.0 versus 19.8 mm Hg (P < .0001). The pump provided an average of 4.0 ± 0.6 L/min of flow for an average duration of 3.7 ± 2.9 days (range, 1.7-12.6). The primary safety endpoint occurred in 2 patients (13%; 1 stroke and 1 death). For the primary efficacy endpoint, recovery of the native heart function was obtained in 93% of the patients discharged, with bridge-to-other-therapy in 7%. Survival to 30 days, 3 months, and 1 year was 94%, 81%, and 75%, respectively. Conclusions: The use of the Impella 5.0/left direct device is safe and feasible in patients presenting with postcardiotomy cardiogenic shock. The device was rapidly inserted, enabled early support, and yielded favorable outcomes. Copyright © 2013 by The American Association for Thoracic Surgery.
Jiang Z.-D.,University of Houston |
Ke S.,Baylor College of Medicine |
DuPont H.L.,St Lukes Episcopal Hospital
International Journal of Antimicrobial Agents | Year: 2010
Rifaximin shortens the duration of travellers' diarrhoea without important alteration of colonic flora. This study investigated the expression of virulence factors [heat-stable (ST) and heat-labile (LT) enterotoxins, surface adhesion factors (CS2/CS3, CS6) and matrix metalloproteinase-9 (MMP-9)] as well as the interleukin (IL)-8 induction potential of diarrhoeagenic Escherichia coli and Shigella sonnei strains exposed to rifaximin (8, 32 and 64 mg/L) for 4, 8, 18 and 24 h. Following exposure to rifaximin, enterotoxigenic E. coli (ETEC) isolates did not express ST/LT, CS2/CS3 or CS6, whereas enteroaggregative E. coli (EAEC) and S. sonnei isolates did not produce detectable amounts of MMP-9. Moreover, induction of IL-8 was undetectable. At subinhibitory concentrations, rifaximin alters the virulence of ETEC, EAEC and S. sonnei isolates. These findings help explain the efficacy of rifaximin despite minimal alteration of colonic flora. © 2009 Elsevier B.V. and the International Society of Chemotherapy.
Hirsch E.B.,University of Houston |
Hirsch E.B.,St Lukes Episcopal Hospital |
Tam V.H.,University of Houston |
Tam V.H.,St Lukes Episcopal Hospital
Journal of Antimicrobial Chemotherapy | Year: 2010
Bacteria producing Klebsiella pneumoniae carbapenemases (KPCs) are rapidly emerging as a cause of multidrug-resistant infections worldwide. Bacterial isolates harbouring these enzymes are capable of hydrolysing a broad spectrum of β-lactams including the penicillins, cephalosporins, carbapenems and monobactam. Detection of isolates harbouring carbapenemases can be inconsistent using automated systems, often requiring subsequent confirmatory tests. Phenotypic methods utilizing boronic acid disc tests have demonstrated promising results and appear practical for use in clinical microbiology laboratories. Treatment of infection caused by KPC bacteria is particularly worrisome as the carbapenems are often agents of the last resort for resistant Gram-negative infections. The optimal treatment of infections caused by KPC bacteria is not well established and clinical outcome data remain sparse. We reviewed the current literature regarding clinical outcomes following KPC infections, with a specific effort to summarize the clinical data available for specific antimicrobial agents. A total of 15 papers involving 55 unique patient cases were reviewed. While the total number of patients is relatively small, some useful insights could still be gathered to guide clinicians in the management of KPC infections. Tigecycline and the aminoglycosides were associated with positive outcomes in the majority of cases. Clinical success rates were low when the polymyxins were used as monotherapy, but were much higher when they were used in combination. Studies examining combination therapy and well-controlled clinical trials are needed to ascertain the optimal treatment of infections caused by KPC bacteria. © The Author 2010. Published by Oxford University Press.
Alpert J.N.,St Lukes Episcopal Hospital
Southern Medical Journal | Year: 2010
A 60-year-old man complained of 20-25 second episodes of bilateral arm paralysis. Neuroimaging disclosed spinal cord compression at the C3-4 level caused by a herniated disc and retrolisthesis. Spinal cord ischemia due to impingement of a vertebral artery or its spinal branch was suspected but could not be substantiated by neuroimaging. Discectomy and fusion eliminated these attacks. © 2010 by The Southern Medical Association.
Terashima T.,Baylor College of Medicine |
Kojima H.,Baylor College of Medicine |
Chan L.,Baylor College of Medicine |
Chan L.,St Lukes Episcopal Hospital
FASEB Journal | Year: 2012
Diabetic neuropathy is the most common diabetic complication. The pathogenetic pathways include oxidative stress, advanced glycation end product (AGE) formation, protein kinase C, and NF-κB activation, as well as increased polyol flux. These metabolic perturbations affect neurons, Schwann cells, and vasa nervorum, which are held to be the primary cell types involved. We hypothesize that diabetes induces the appearance of abnormal bone marrow-derived cells (BMDCs) that fuse with neurons in the dorsal root ganglia (DRG) of mice, leading to diabetic neuropathy. Neuronal poly(ADP-ribose) polymerase-1 (PARP-1) activation in diabetes is known to generate free radical and oxidant-induced injury and poly(ADP-ribose) polymer formation, resulting in neuronal death and dysfunction, culminating in neuropathy. We further hypothesize that BM-specific PARP expression plays a determining role in disease pathogenesis. Here we show that bone marrow transplantation (BMT) of PARP-knockout (PARPKO) cells to wild-type mice protects against, whereas BMT of wild-type cells to PARPKO mice, which are normally "neuropathy-resistant, " confers susceptibility to, diabetic neuropathy. The pathogenetic process involving hyperglycemia, BMDCs, and BMDC-neuron fusion can be recapitulated in vitro. Incubation in high, but not low, glucose confers fusogenicity to BMDCs, which are characterized by proinsulin (PI) and TNF-α coexpression; coincubation of isolated DRG neurons with PI-BMDCs in high glucose leads to spontaneous fusion between the 2 cell types, while the presence of a PARP inhibitor or use of PARPKO BMDCs in the incubation protects against BMDC-neuron fusion. These complementary in vivo and in vitro experiments indicate that BMDC-PARP expression promotes diabetic neuropathy via BMDC-neuron fusion. © FASEB.
Chen W.,Baylor College of Medicine |
Chang B.,Baylor College of Medicine |
Li L.,Baylor College of Medicine |
Chan L.,Baylor College of Medicine |
Chan L.,St Lukes Episcopal Hospital
Hepatology | Year: 2010
PNPLA3 (adiponutrin), a novel patatin-like phospholipase domain-containing enzyme, is expressed at high level in fat, but also in other tissues including liver. Polymorphisms in PNPLA3 have been linked to obesity and insulin sensitivity. Notably, a nonsynonymous variant rs738409(G) allele of the PNPLA3 gene was found to be strongly associated with both nonalcoholic and alcoholic fatty liver disease. We have generated Pnpla3-/- mice by gene targeting. Loss of Pnpla3 has no effect on body weight or composition, adipose mass, or development, whether the mice were fed regular chow or high-fat diet or bred into the genetic obese Lepob/ob background. Plasma and liver triglyceride content and plasma aspartate aminotransferase and alanine aminotransferase levels were not different between Pnpla3+/+ and Pnpla3-/- mice while they were on regular chow, fed three different fatty liver-inducing diets, or after they were bred into Lepob/ob background. Hepatic Pnpla5 messenger RNA (mRNA) levels were similar in wild-type and Pnpla3-/- mice, although adipose Pnpla5 mRNA level was increased in Pnpla3-/- mice. A high-sucrose lipogenic diet stimulated hepatic Pnpla3 and Pnpla5 mRNA levels to a similar degree, but it did not affect adipose or liver triglyceride lipase (ATGL, known also as Pnpla2) mRNA in Pnpla3 +/+ and Pnpla3-/- mice. Finally, Pnpla3+/+ and Pnpla3-/- mice displayed similar glucose tolerance and insulin tolerance tests while on regular chow or three different fatty liver-inducing diets. Conclusion: Loss of Pnpla3 does not cause fatty liver, liver enzyme elevation, or insulin resistance in mice. Copyright © 2010 by the American Association for the Study of Liver Diseases.
Bavishi C.,University of Texas Health Science Center at Houston |
DuPont H.L.,University of Texas Health Science Center at Houston |
DuPont H.L.,St Lukes Episcopal Hospital |
DuPont H.L.,Baylor College of Medicine
Alimentary Pharmacology and Therapeutics | Year: 2011
Background The use of proton pump inhibitors (PPIs) is increasing worldwide. Suppression of gastric acid alters the susceptibility to enteric bacterial pathogens. Aim This systematic review was undertaken to examine the relationship between PPI use and susceptibility to enteric infections by a specific pathogen based on published literature and to discuss the potential mechanisms of PPI enhanced pathogenesis of enteric infections. Methods PubMed, OVID Medline Databases were searched. Search terms included proton pump inhibitors and mechanisms of, actions of, gastric acid, enteric infections, diarrhoea, Clostridium difficile, Salmonella, Shigella and Campylobacter. Results The use of PPIs increases gastric pH, encourages growth of the gut microflora, increases bacterial translocation and alters various immunomodulatory and anti-inflammatory effects. Enteric pathogens show variable gastric acid pH susceptibility and acid tolerance levels. By multiple mechanisms, PPIs appear to increase susceptibility to the following bacterial enteropathogens: Salmonella, Campylobacter jejuni, invasive strains of Escherichia coli, vegetative cells of Clostridium difficile, Vibrio cholerae and Listeria. We describe the available evidence for enhanced susceptibility to enteric infection caused by Salmonella, Campylobacter and C. difficile by PPI use, with adjusted relative risk ranges of 4.2-8.3 (two studies); 3.5-11.7 (four studies); and 1.2-5.0 (17 of 27 studies) for the three respective organisms. Conclusions Severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increased susceptibility to enteric bacterial infection. The clinical implication of chronic PPI use among hospitalized patients placed on antibiotics and travellers departing for areas with high incidence of diarrhoea should be considered by their physicians. © 2011 Blackwell Publishing Ltd.
Appell R.A.,Baylor College of Medicine |
Appell R.A.,St Lukes Episcopal Hospital
Urologic Clinics of North America | Year: 2011
Stress urinary incontinence (SUI) and urge incontinence (UI) are increasingly significant health concerns for millions of women. Investigation continues into the use of different types of procedures for the surgical management of UI that can be done in the ambulatory office without the use of general or regional anesthesia. Injectable treatment for SUI and UI lend themselves to the ambulatory or office setting and mimic the efficacy and safety profiles of currently available procedures. © 2011 Elsevier Inc.
Yang Y.,Baylor College of Medicine |
Chang B.H.-J.,Baylor College of Medicine |
Chan L.,Baylor College of Medicine |
Chan L.,St Lukes Episcopal Hospital
EMBO Molecular Medicine | Year: 2013
Genome-wide association studies identified GLIS3 as a susceptibility locus for type 1 and type 2 diabetes. Global Glis3 deficiency in mice leads to congenital diabetes and neonatal lethality. In this study, we explore the role of Glis3 in adulthood using Glis3+/- and conditional knockout animals. We challenged Glis3+/- mice with high fat diet for 20 weeks and found that they developed diabetes because of impaired beta cell mass expansion. GLIS3 controls beta cell proliferation in response to high-fat feeding at least partly by regulating Ccnd2 transcription. To determine if sustained Glis3 expression is essential to normal beta cell function, we generated Glis3fl/fl/Pdx1CreERT+ animal by intercrossing Glis3fl/fl mice with Pdx1CreERT+ mice and used tamoxifen (TAM) to induce Glis3 deletion in adults. Adult Glis3fl/fl/Pdx1CreERT+ mice are euglycaemic. TAM-mediated beta cell-specific inactivation of Glis3 in adult mice downregulates insulin expression, leading to hyperglycaemia and subsequently enhanced beta cell apoptosis. We conclude that normal Glis3 expression is required for pancreatic beta cell function and mass maintenance during adulthood, which impairment leads to diabetes in adults. © 2012 The Authors.
St Lukes Episcopal Hospital and University of Houston | Date: 2013-05-06
In some embodiments, the present disclosure pertains to a method of delivery of an active agent to a target tissue, in a subject in need thereof comprising positioning a high intensity focused ultrasound transducer to enable delivery of ultrasound energy to the target tissue. Such a method comprises energizing the high intensity focused ultrasound transducer; imaging at least a portion of the target tissue; and discontinuing delivery of ultrasound energy. Further, such a method may comprise administering the active agent to the subject under the conditions of thermal stimulation. In another embodiment, the present disclosure relates to a method of treating a tumor in a subject in need thereof comprising administering a therapeutic agent to the subject and providing thermal stimulation to the tumor. In some embodiments, there is provided a method for increasing the efficacy of a therapeutic agent in a target tissue.