Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
Acta Pharmacol Sin ; 42(4): 508-517, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32724175

ABSTRACT

Hypertension is the most prevalent health condition worldwide, affecting ~1 billion people. Gordon's syndrome is a form of secondary hypertension that can arise due to a number of possible mutations in key genes that encode proteins in a pathway containing the With No Lysine [K] (WNK) and its downstream target kinases, SPS/Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress responsive kinase 1 (OSR1). This pathway regulates the activity of the thiazide-sensitive sodium chloride cotransporter (NCC), which is responsible for NaCl reabsorption in the distal nephron. Therefore, mutations in genes encoding proteins that regulate the NCC proteins disrupt ion homeostasis and cause hypertension by increasing NaCl reabsorption. Thiazide diuretics are currently the main treatment option for Gordon's syndrome. However, they have a number of side effects, and chronic usage can lead to compensatory adaptations in the nephron that counteract their action. Therefore, recent research has focused on developing novel inhibitory molecules that inhibit components of the WNK-SPAK/OSR1-NCC pathway, thereby reducing NaCl reabsorption and restoring normal blood pressure. In this review we provide an overview of the currently reported molecular inhibitors of the WNK-SPAK/OSR1-NCC pathway and discuss their potential as treatment options for Gordon's syndrome.


Subject(s)
Protein Kinase Inhibitors/therapeutic use , Pseudohypoaldosteronism/drug therapy , Signal Transduction/drug effects , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Animals , Blood Pressure/drug effects , Calcium-Binding Proteins/antagonists & inhibitors , Cullin Proteins/antagonists & inhibitors , Diuretics/therapeutic use , Humans , Microfilament Proteins/antagonists & inhibitors , Protein Binding/drug effects , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/metabolism , Pseudohypoaldosteronism/metabolism , Signal Transduction/physiology , Solute Carrier Family 12, Member 3/metabolism , WNK Lysine-Deficient Protein Kinase 1/antagonists & inhibitors , WNK Lysine-Deficient Protein Kinase 1/metabolism
2.
JACC Clin Electrophysiol ; 3(6): 623-631, 2017 06.
Article in English | MEDLINE | ID: mdl-29759437

ABSTRACT

OBJECTIVES: This study sought to develop a validated, reproducible sterilization protocol, which could be used in the reprocessing of cardiac implantable electronic devices (CIEDs). BACKGROUND: Access to cardiac CIED therapy in high-income and in low- and middle-income countries varies greatly. CIED reuse may reduce this disparity. METHODS: A cleaning and sterilization protocol was developed that includes washing CIEDs in an enzymatic detergent, screw cap and set screw replacement, brushing, inspection, and sterilization in ethylene oxide. Validation testing was performed to assure compliance with accepted standards. RESULTS: With cleaning, the total mean bioburden for each of 3 batches of 10 randomly chosen devices was reduced from 754 to 10.1 colony-forming units. After sterilization with ethylene oxide, with 3 half-cycle and 3 full-cycle processes, none of the 90 biological indicator testers exhibited growth after 7 days. Through cleaning and sterilization, protein and hemoglobin concentrations were reduced from 99.2 to 1.42 µg/cm2 and from 21.4 to 1.03 µg/cm2, respectively. Mean total organic carbon residual was 1.44 parts per million (range 0.36 to 2.9 parts per million). Endotoxin concentration was not detectable at the threshold of <0.03 endotoxin units/ml or <3.0 endotoxin units/device. Cytotoxicity and intracutaneous reactivity tests met the standards set by the Association for Advancement of Medical Instrumentation and the International Organization for Standardization. CONCLUSIONS: CIEDs can be cleaned and sterilized according to a standardized protocol achieving a 12-log reduction of inoculated product, resulting in sterility assurance level of 10-6.


Subject(s)
Defibrillators, Implantable , Equipment Reuse , Sterilization , Detergents/therapeutic use , Equipment Reuse/standards , Humans , Reproducibility of Results , Sterilization/methods , Sterilization/standards
3.
Ochsner J ; 15(1): 106-9, 2015.
Article in English | MEDLINE | ID: mdl-25829891

ABSTRACT

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAAION) has a poorly understood etiology, and the onset of simultaneous bilateral NAAION in a patient <50 years without identifiable systemic risk factors is rare. CASE REPORT: We present the case of a patient with acute painless monocular vision loss and bilateral optic disc edema who subsequently developed painless vision loss in the fellow eye. The patient's history was significant for diffuse large B-cell lymphoma, and our pressing diagnostic concern was to determine if his vision loss and bilateral optic disc changes represented lymphomatous infiltrates. A complete ocular exam demonstrated findings consistent with simultaneous bilateral NAAION. After an extensive systemic workup for malignancy with central nervous system involvement, vasculitis, and other entities associated with NAAION, we determined that the patient's primary risk factor for developing bilateral ischemic optic neuropathies was his crowded optic discs. CONCLUSION: This case supports the hypothesis that a crowded optic disc is a sufficient primary risk factor for developing NAAION.

4.
Ochsner J ; 13(4): 553-7, 2013.
Article in English | MEDLINE | ID: mdl-24358007

ABSTRACT

BACKGROUND: Multiple myeloma is a common disease, accounting for about 10% of hematologic malignancies in the United States. For eligible patients, the treatment of choice includes induction therapy (usually involving newer biologic agents) followed by autologous stem cell transplant; however, this treatment is generally not considered curative, and relapses usually occur. However, extramedullary relapse is an uncommon presentation, and relapses that involve the lungs have only rarely been described. CASE REPORT: We report the case of a patient who underwent an autologous stem cell transplant for multiple myeloma and subsequently relapsed with diffuse pulmonary nodules. She then had a rapid clinical and serologic response following initiation of salvage therapy. CONCLUSION: This case is remarkable for both the radiographic appearance of the pulmonary involvement, as well as the rapid resolution of these findings after 2 cycles of treatment with bortezomib, dexamethasone, and lenalidomide.

6.
J Clin Oncol ; 28(27): 4207-13, 2010 Sep 20.
Article in English | MEDLINE | ID: mdl-20713865

ABSTRACT

PURPOSE: Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid. PATIENTS AND METHODS: Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5). Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid ≤ 7.5 mg/dL during days 3 to 7. RESULTS: Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol. Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015). Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol. CONCLUSION: In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol. Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol.


Subject(s)
Allopurinol/therapeutic use , Antineoplastic Agents/adverse effects , Hematologic Neoplasms/drug therapy , Hyperuricemia/drug therapy , Tumor Lysis Syndrome/drug therapy , Urate Oxidase/therapeutic use , Uric Acid/blood , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Allopurinol/administration & dosage , Allopurinol/adverse effects , Biomarkers/blood , Drug Therapy, Combination , Female , Humans , Hyperuricemia/blood , Hyperuricemia/etiology , Infusions, Intravenous , Male , Middle Aged , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Tumor Lysis Syndrome/blood , Tumor Lysis Syndrome/etiology , United States , Urate Oxidase/administration & dosage , Urate Oxidase/adverse effects , Young Adult
7.
Ochsner J ; 8(1): 4, 2008.
Article in English | MEDLINE | ID: mdl-21603549
8.
Cancer ; 100(4): 746-50, 2004 Feb 15.
Article in English | MEDLINE | ID: mdl-14770430

ABSTRACT

BACKGROUND: The current study determined the efficacy and toxicity of weekly paclitaxel in combination with estramustine phosphate (EMP) in patients with androgen-independent prostate carcinoma (AIPC). METHODS: Patients with progressive AIPC received 90 mg/m2 paclitaxel by 1-hour intravenous infusion weekly for 3 weeks, followed by a 1-week treatment rest. Patients received 140 mg EMP orally 3 times daily on the day before, the day of, and the day after paclitaxel administration. Patients received 1 mg warfarin daily to prevent thromboembolism. RESULTS: Sixty-six patients with progressive AIPC received treatment at 29 centers. Forty-two percent of patients had a 50% decline in prostate-specific antigen (PSA; 95% confidence interval [CI], 30-54%). For 26 patients with bidimensionally measurable disease, the objective response rate was 15% (95% CI, 1-30%). The median time to disease progression was 6.3 months, and the median time to PSA progression was 11.4 months. The median survival period was 15.6 months. Grade 3-4 toxicities were uncommon and included thromboembolism (8%), anemia (3%), neutropenia (3%), and peripheral neuropathy (2%). There was one treatment-related death. CONCLUSIONS: This regimen of EMP plus weekly paclitaxel was an active and well tolerated treatment for patients with AIPC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Androgens/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma/pathology , Drug Administration Schedule , Estramustine/administration & dosage , Humans , Infusions, Intravenous , Male , Middle Aged , Paclitaxel/administration & dosage , Prostatic Neoplasms/pathology , Survival Analysis , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...