Now showing items 21-35 of 35

    • Plerixafor Salvage Is Safe and Effective in Hard-to-Mobilize Patients Undergoing Chemotherapy and Filgrastim-Based Peripheral Blood Progenitor Cell Mobilization

      Awan, Farrukh T.; Kochuparambil, S. Thomas; DeRemer, David; Cumpston, Aaron; Craig, Michael; Jillella, Anand; Hamadani, Mehdi; Department of Medicine; Department of Pharmacology and Toxicology (2012-04-10)
      The combination of filgrastim (G-CSF) and plerixafor is currently approved for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin lymphoma and multiple myeloma undergoing autologous peripheral blood hematopoietic cell transplantation. However, chemotherapy and G-CSF-based mobilization remains a widely used strategy for peripheral blood progenitor cell collection. In this paper we describe our experience from two North American transplant centers in a series of patients who received salvage plerixafor while failing chemotherapy and G-CSF mobilization. Patients received a median of two doses of plerixafor salvage upon failure to mobilize adequate number of peripheral blood progenitor cells at neutrophil recovery. The use of plerixafor was associated with a 2.4-fold increase in peripheral blood CD34+ cell count and 3.9-fold increase in total CD34+ cell yield. All patients were able to collect â ¥2 Ã 106 CD34+â cells/kg with this approach. These results were more pronounced in patients with a higher CD34+ cell count at the time of the first plerixafor dose. Interestingly, peripheral blood white blood cell count was not shown to correlate with a response to plerixafor. Our results provide safety and efficacy data for the use of plerixafor in patients who are destined to fail chemomobilization.
    • Carcinomatous Meningitis: The Natural History of Successfully Treated Metastatic Bladder Cancer

      Tadepalli, S.; Coleman, Teresa; Hackett, Ladawn A.; Liles, G.B.; Department of Medicine; Department of Pathology (2011-08-24)
      Carcinomatous meningitis due to bladder cancer is a rare entity reported only in case reports. Optimal therapy is thus poorly defined with earlier cases reporting an unsuccessful outcome. Here we report a case of late carcinomatous meningitis secondary to transitional cell carcinoma (TCC) of the bladder occurring in a patient in complete remission. He was successfully treated with intrathecal methotrexate and whole brain irradiation and experienced prolonged survival after treatment. With modern chemotherapy increasing complete remissions and survival rates in patients with TCC, more and more patients are being reported with carcinomatous meningitis. We raise the question of whether central nervous system prophylaxis should be considered in patients with TCC achieving a complete remission to chemotherapy in the metastatic setting.
    • Improved Immunodetection of Endogenous α-Synuclein

      Lee, Byung Rho; Kamitani, Tetsu; Department of Medicine; Center for Molecular Chaperone/Radiobiology & Cancer Virology (2011-08-19)
      α-Synuclein is a key molecule in understanding the pathogenesis of neurodegenerative α-synucleinopathies such as Parkinson's disease. Despite extensive research, however, its precise function remains unclear partly because of a difficulty in immunoblotting detection of endogenous α-synuclein. This difficulty has largely restricted the progress for α-synucleinopathy research. Here, we report that α-synuclein monomers tend to easily detach from blotted membranes, resulting in no or very poor detection. To prevent this detachment, a mild fixation of blotted membranes with paraformaldehyde was applied to the immunoblotting method. Amazingly, this fixation led to clear and strong detection of endogenous α-synuclein, which has been undetectable by a conventional immunoblotting method. Specifically, we were able to detect endogenous α-synuclein in various human cell lines, including SH-SY5Y, HEK293, HL60, HeLa, K562, A375, and Daoy, and a mouse cell line B16 as well as in several mouse tissues such as the spleen and kidney. Moreover, it should be noted that we could clearly detect endogenous α-synuclein phosphorylated at Ser-129 in several human cell lines. Thus, in some tissues and cultured cells, endogenous α-synuclein becomes easily detectable by simply fixing the blotted membranes. This improved immunoblotting method will allow us to detect previously undetectable endogenous α-synuclein, thereby facilitating α-synuclein research.
    • Mild Functional Ischemic Mitral Regurgitation Following Acute Coronary Syndrome: A Retrospective Study

      Pant, Sadip; Neupane, Pritam; Pant, Om Biju; Paudel, Raju; Kumar, M. P. Kavin; Vijayashankar, C. S.; Shrestha, Rajendra Man; Department of Pulmonary and Critical Care (2011-04)
      Background:: Ischemic mitral regurgitation is a frequent complication of acute coronary syndrome. It primarily occurs in patients with a prior myocardial infarction but also may be seen with acute ischemia, a setting in which the MR typically resolves after the ischemia resolves. The vast majority of patients have â functionalâ ischemic MR. In these individuals, the papillary muscles, chordae, and valve leaflets are normal. However, the leaflets do not coapt and restricted leaflet motion is frequently noted on echocardiography. Ischemic mitral regurgitation indicates a poor prognosis after acute myocardial infarction. This study addresses the clinical characteristics of patients of acute coronary syndrome with mild functional ischemic mitral regurgitation and its impact on immediate in-hospital cardiovascular outcomes and death.
    • PROTEIN SYNTHESIS IN PANCREAS OF FASTED PIGEONS

      Black, Owen; Webster, Paul D.; Department of Medicine; Department of Cellular Biology and Anatomy (1973-04-1)
      The regulation of protein synthesis in the pigeon has been studied by comparing the capability of cell-free amino acid incorporating systems of membrane-bound and membrane-free polysomes prepared from fasted and fed birds. New methods were developed for isolating polysomes since techniques used for other tissues did not provide quantitative recovery of polysomal RNA. The sucrose gradient profile of polysomes from pigeon pancreas showed a predominance of trisome species. Although initiation factors are present on polysomes, it was found that polysomes in cell-free systems would not initiate protein synthesis without exogenous initiation factors. This suggested the presence of an inhibitor or regulator of protein synthesis. These studies show that fasting resulted in: (a) decreased amounts of polysomes; (b) disaggregation of polysomes to monosomes; (c) decreased capability of polysomes to synthesize nascent peptides and to initiate additional synthesis, apparently not related to concentration of initiation factors.
    • The effect of student training on accuracy of completion of death certificates.

      Degani, Adil T; Patel, Rajendrakumar M; Smith, Betsy E; Grimsley, Edwin; Section of Pulmonary & Critical Care Medicine, Department of Medicine, Medical College of Georgia (2010-02-18)
      BACKGROUND: Death certificates are an invaluable source of statistical and medical information, as well as important legal documents. However, few physicians receive formal training on how to accurately complete them. PURPOSE: To determine if a simple intervention can improve the accuracy of death certificate completion by medical students. METHODS: Participants included all third year medical students undergoing their core Internal Medicine rotation at Mercer University School of Medicine at the Medical Center of Central Georgia. Participation was voluntary and participants completed an approved informed consent. Students were presented a tutorial from the National Association of Medical Examiners website. They were asked to complete a death certificate both before and after the tutorial along with subjective questionnaires. The primary outcome measurement was the difference in scores pre- and post-tutorial. RESULTS: The mean score before the tutorial was 11.75 (+/-3.20) and the mean score post-tutorial was 18.85 (+/-2.56), indicating an increase in scores. The mean difference in pre- and post-tutorial scores was significant (t = 20.39, p < 0.0001). CONCLUSIONS: We found that using a tutorial to teach students how to correctly complete a death certificate was effective.
    • Impact of clinical pharmacy services on renal transplant recipients' adherence and outcomes.

      Chisholm-Burns, Marie A; Spivey, Christina A; Garrett, Charlene; McGinty, Herbert; Mulloy, Laura L; Department of Medicine (2009-11-20)
      The purpose of this article is to provide a description of a clinical pharmacy services program implemented in a renal transplant clinic to improve medication access and adherence as well as health and economic outcomes among renal transplant recipients (RTRs). Following a team-based planning process and an informal survey of RTRs, a clinical pharmacy service intervention was implemented in the Medical College of Georgia renal transplant clinic. As part of the intervention, a clinical pharmacist reviewed and optimized medication therapy, provided instructions on how to take medication, and assisted with enrollment into medication assistance programs. Significant differences were found between RTRs who did and did not receive clinical pharmacy services on measures of adherence, health, economics, and quality of life. Clinical pharmacy services, as described in this article, have a positive impact on renal transplant recipients' medication adherence, health and economic outcomes, and health-related quality of life. The findings described here suggest that clinical pharmacy services are a viable and effective option for improving care for RTRs in an outpatient clinic setting.
    • Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants?

      Dodani, Sunita; Dong, Yanbin; Zhu, Haidong; George, Varghese; Department of Medicine (2010-03-19)
      Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.
    • Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report.

      Sachdeva, Alok; Goeckeritz, Bruce E; Oliver, Alyce M; Department of Medicine (2008-08-21)
      ABSTRACT: Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10-20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden.
    • The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.

      Pedersen-White, Jennifer R; Chorich, Lynn P; Bick, David P; Sherins, Richard J; Layman, Lawrence C; Department of Medicine; Department of Obstetrics and Gynecology; Department of Obstetrics and Gynecology; Institute of Molecular Medicine and Genetics; Institute of Neuroscience (2008-06-23)
      Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH). Mutations in three genes--KAL1, GNRHR and FGFR1--account for 15-20% of all causes of IHH/KS. Nearly all mutations are point mutations identified by traditional PCR-based DNA sequencing. The relatively new method of multiplex ligation-dependent probe amplification (MLPA) has been successful for detecting intragenic deletions in other genetic diseases. We hypothesized that MLPA would detect intragenic deletions in approximately 15-20% of our cohort of IHH/KS patients. Fifty-four IHH/KS patients were studied for KAL1 deletions and 100 were studied for an autosomal panel of FGFR1, GNRH1, GNRHR, GPR54 and NELF gene deletions. Of all male and female subjects screened, 4/54 (7.4%) had KAL1 deletions. If only anosmic males were considered, 4/33 (12.1%) had KAL1 deletions. No deletions were identified in any of the autosomal genes in 100 IHH/KS patients. We believe this to be the first study to use MLPA to identify intragenic deletions in IHH/KS patients. Our results indicate approximately 12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.
    • 8-Cl-Adenosine enhances 1,25-dihydroxyvitamin D3-induced growth inhibition without affecting 1,25-dihydroxyvitamin D3-stimulated differentiation of primary mouse epidermal keratinocytes.

      Bollag, Wendy B; Zhong, Xiaofeng; Josephson, Sarah; Department of Medicine; Department of Cellular Biology and Anatomy; Institute of Molecular Medicine and Genetics (2004-08-10)
      BACKGROUND: Epidermal keratinocytes continuously proliferate and differentiate to form the mechanical and water permeability barrier that makes terrestrial life possible. In certain skin diseases, these processes become dysregulated, resulting in abnormal barrier formation. In particular, skin diseases such as psoriasis, actinic keratosis and basal and squamous cell carcinomas are characterized by hyperproliferation and aberrant or absent differentiation of epidermal keratinocytes. We previously demonstrated that 8-Cl-adenosine (8-Cl-Ado) can induce keratinocyte growth arrest without inducing differentiation. RESULTS: To determine if this agent might be useful in treating hyperproliferative skin disorders, we investigated whether 8-Cl-Ado could enhance the ability of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], a known keratinocyte differentiating agent and a clinical treatment for psoriasis, to inhibit keratinocyte growth. We found that low concentrations of 8-Cl-Ado and 1,25(OH)2D3 appeared to act additively to reduce proliferation of primary mouse epidermal keratinocytes. However, another agent (transforming growth factor-beta) that triggers growth arrest without inducing differentiation also coincidentally inhibits differentiation elicited by other agents; inhibition of differentiation is suboptimal for treating skin disorders, as differentiation is often already reduced. Thus, we determined whether 8-Cl-Ado also decreased keratinocyte differentiation induced by 1,25(OH)2D3, as measured using the early and late differentiation markers, keratin 1 protein levels and transglutaminase activity, respectively. 8-Cl-Ado did not affect 1,25(OH)2D3-stimulated keratin 1 protein expression or transglutaminase activity. CONCLUSIONS: Our results suggest that 8-Cl-Ado might be useful in combination with differentiating agents for the treatment of hyperproliferative disorders of the skin.
    • An unusual case of peripartum cardiomyopathy manifesting with multiple thrombo-embolic phenomena.

      Ibebuogu, Uzoma N; Thornton, John W; Reed, Guy L; Department of Medicine (2007-12-31)
      ABSTRACT: Peripartum cardiomyopathy (PPCM) is a rare form of heart failure with a reported incidence of 1 per 3000 to 1 per 4000 live births and a fatality rate of 20%-50%. Onset is usually between the last month of pregnancy and up to 5 months postpartum in previously healthy women. Although viral, autoimmune and idiopathic factors may be contributory, its etiology remains unknown. PPCM initially presents with signs and symptoms of congestive heart failure and rarely with thrombo-embolic complications. We report an unusual case of PPCM in a previously healthy postpartum woman who presented with an acute abdomen due to unrecognized thromboemboli of the abdominal organs. This case illustrates that abdominal pain in PPCM may not always result from hepatic congestion as previously reported, but may occur as a result of thromboemboli to abdominal organs. Further research is needed to determine the true incidence of thromboemboli in PPCM.
    • Excess coronary artery disease risk in South Asian immigrants: can dysfunctional high-density lipoprotein explain increased risk?

      Dodani, Sunita; Department of Medicine (2009-02-02)
      BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. DISCUSSION: The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. CONCLUSIONS: More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.
    • Rab proteins in gastric parietal cells: evidence for the membrane recycling hypothesis.

      Calhoun, Benjamin C; Goldenring, J R; Department of Medicine (1997-07-08)
      The gastric parietal cell secretes large quantities of HCl into the lumen of the gastric gland in response to secretagogues such as histamine. In the membrane recycling hypothesis, this secretory activity requires the trafficking of the gastric H+/K(+)-ATPase to the cell surface from intracellular tubulovesicles. The Rab subclass of small GTP-binding proteins is thought to confer specificity to vesicle transport throughout the secretory pathway, and previous investigations established that Rab11 is highly expressed in gastric parietal cells. Recent discoveries in intra-Golgi transport and neuronal synaptic vesicle fusion have fortuitously converged on an evolutionarily conserved protein complex involved in vesicle docking and fusion. Recent results indicate that Rab11 is involved in the apical targeting of vesicles in parietal cells and other epithelial cells throughout the gastrointestinal tract. In support of the membrane recycling hypothesis, Rab co-segregates with H+/K(+)-ATPase in parietal cells. The presence of Rab11 on tubulovesicles supports a role for this Rab protein in recycling vesicle trafficking.
    • Hydrogen peroxide improves the visibility of ulcer bases in acute non-variceal upper gastrointestinal bleeding: a single-center prospective study.

      Sridhar, Subbaramiah; Chamberlain, Sherman; Thiruvaiyaru, Dharma; Sethuraman, Sankara; Patel, Jigneshkumar; Schubert, Moonkyung; Cuartas-Hoyos, Francisco; Schade, Robert R.; Department of Medicine (2009-10-19)
      BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (ANVB) or hemorrhage (used interchangeably) is an emergency. Endoscopically applied hydrogen peroxide (H2O2) has been shown to improve visualization of the ulcer base. AIMS: To test the hypothesis that ulcer base clot clearance with 3% H2O2 improves the visualization of ANVB lesions compared to water alone. METHODS: In this single-center prospective study, 320 patients with ANVB were examined, of which 81 met the entry criteria for evaluation. All patients with ANVB underwent urgent endoscopy. Those with adherent clots on the ulcer base were sprayed with 250 ml of water, followed by up to 100 ml of 3% H2O2. The main outcome measurement was Kalloo"s Visual Scores of the ulcer base before and after water and H2O2. RESULTS: Eighty-one patients with gastric ulcers (GU; 34) and duodenal ulcers (DU; 47) met the entry criteria. The mean improvement in grade from water to H2O2 was 2.04 (95% confidence interval [CI] (1.86, 2.23)). The mean volume of H2O2 used to clear clots was higher (70 ml) in patients who were negative for both Helicobacter pylori and non-steroidal anti-inflammatory drug (NSAID) use than in those who were positive for both (31 ml) (P = 0.00). More DU patients (72%) had visible vessels than GU patients (44%) (P = 0.01). CONCLUSIONS: H2O2 improved the visualization of ulcer bases in ANVB. A smaller volume of H2O2 was required to clear clots in patients who used NSAIDs and had H. pylori infection. H2O2 identified more DU vessels. The use of H2O2 should be considered as a standard therapy in the management of clots in ANVB.