Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Language
Publication year range
1.
J Neurosurg Case Lessons ; 7(13)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38531080

ABSTRACT

BACKGROUND: Isolated cerebral mucormycosis is rare in immunocompetent adults and is only sparsely reported to be associated with obstructive hydrocephalus. OBSERVATIONS: Here, the authors report a case of obstructive hydrocephalus secondary to central nervous system mucormycosis without other systems or rhino-orbital involvement and its technical surgical management. A 23-year-old, incarcerated, immunocompetent patient with history of intravenous (IV) drug use presented with syncope. Although clinical and radiographic findings failed to elucidate an infectious pathology, endoscopy revealed an obstructive mass lesion at the level of the third ventricle, which, on microbiological testing, was confirmed to be Rhizopus fungal ventriculitis. Perioperative cerebrospinal fluid diversion, endoscopic third ventriculostomy, endoscopic biopsy technique, patient outcomes, and the literature are reviewed here. The patient received intrathecal and IV amphotericin B followed by a course of oral antifungal treatment and currently remains in remission. LESSONS: The patient's unique presentation and diagnosis of isolated cerebral mucormycosis reveal this pathogen as a cause of ventriculitis and obstructive hydrocephalus in immunocompetent adult patients, even in the absence of infectious sequelae on neuroimaging.

3.
Ann Card Anaesth ; 23(4): 447-452, 2020.
Article in English | MEDLINE | ID: mdl-33109802

ABSTRACT

Context: The concomitant use of cuffed endotracheal tubes (ETT) and transesophageal echocardiography (TEE) probes increases ETT cuff pressures (CP), which may contribute to mucosal ischemia and perioperative complications such as failed extubation. Aims: To assess changes in ETT CP after TEE insertion in patients of different age groups undergoing congenital heart surgery and examine the relationship between ETT CP and postoperative extubation failure. Settings and Design: Single-center quality improvement project. Subjects and Methods: ETT CP was measured with a manometer following intubation and again after TEE insertion. Tracheal perfusion pressure was then calculated and postoperative extubation failures were recorded. Statistical Analysis: Chi-square testing, Fisher's-exact testing, one-way analysis of variance testing or Kruskal-Wallis testing with Dunn's pairwise, and student's t-test or Wilcoxon rank-sum testing were used to analyze the data. Results: Median ETT CP increased significantly after TEE insertion in each age group, with infants showing a smaller magnitude of increase (+2 [1-6] cm H2O, P < 0.001) than adults (+12 [8-14] cm H2O, P = 0.008) (intergroup comparison P = 0.002). Five patients (9%) failed extubation, all of which were infants. Within the infant subgroup, no significant difference existed between failed vs successful extubation regarding ETT CP during bypass (15 ± 1 vs 16 ± 2 mmHg, P = 0.206) or tracheal perfusion pressure pre-bypass (34 ± 9 vs 38 ± 11 mmHg, P = 0.518), during bypass (20 ± 9 vs 22 ± 6 mmHg, P = 0.697), or post-bypass (42 ± 9 vs 41 ± 9 mmHg, P = 0.923). There was a significant difference in cardiopulmonary bypass duration (151 ± 29 vs 85 ± 32 min, P < 0.001). Conclusion: Factors beyond intraoperative ETT CP likely play a larger role in postoperative extubation failure.


Subject(s)
Airway Extubation , Cardiac Surgical Procedures , Intubation, Intratracheal , Adolescent , Adult , Cardiopulmonary Bypass , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Trachea/diagnostic imaging
4.
Hum Mol Genet ; 28(24): 4132-4147, 2019 12 15.
Article in English | MEDLINE | ID: mdl-31646342

ABSTRACT

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, characterized by cyst formation and growth. Hyperproliferation is a major contributor to cyst growth. At the nexus of regulating proliferation, is 4E-BP1. We demonstrate that ADPKD mouse and rat models, ADPKD patient renal biopsies and PKD1-/- cells exhibited hyperphosphorylated 4E-BP1, a biomarker of increased translation and proliferation. We hypothesized that expression of constitutively active 4E-BP1 constructs (4E-BP1F113A and 4E-BP1R13AF113A) would decrease proliferation and reduce cyst expansion. Utilizing the Pkd1RC/RC mouse, we determined the effect of 4E-BP1F113A on PKD. Unexpectedly, 4E-BP1F113A resulted in increased cyst burden and suppressed apoptosis markers, increased anti-apoptotic Bcl-2 protein and increased mitochondrial proteins. Exogenous 4E-BP1 enhanced proliferation, decreased apoptosis, increased anti-apoptotic Bcl-2 protein, impaired NADPH oxidoreductase activity, increased mitochondrial proteins and increased superoxide production in PKD patient-derived renal epithelial cells. Reduced 4E-BP1 expression suppressed proliferation, restored apoptosis and improved cellular metabolism. These findings provide insight into how cyst-lining cells respond to 4E-BP1.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cell Cycle Proteins/metabolism , Polycystic Kidney Diseases/metabolism , Polycystic Kidney, Autosomal Dominant/metabolism , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Male , Mice , NADH, NADPH Oxidoreductases/metabolism , Phosphorylation , Polycystic Kidney Diseases/pathology , Polycystic Kidney, Autosomal Dominant/pathology , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , Rats , TRPP Cation Channels/metabolism
5.
Int J Mol Sci ; 20(12)2019 Jun 20.
Article in English | MEDLINE | ID: mdl-31226747

ABSTRACT

Cisplatin is a widely used chemotherapeutic agent used to treat solid tumours, such as ovarian, head and neck, and testicular germ cell. A known complication of cisplatin administration is acute kidney injury (AKI). The development of effective tumour interventions with reduced nephrotoxicity relies heavily on understanding the molecular pathophysiology of cisplatin-induced AKI. Rodent models have provided mechanistic insight into the pathophysiology of cisplatin-induced AKI. In the subsequent review, we provide a detailed discussion of recent advances in the cisplatin-induced AKI phenotype, principal mechanistic findings of injury and therapy, and pre-clinical use of AKI rodent models. Cisplatin-induced AKI murine models faithfully develop gross manifestations of clinical AKI such as decreased kidney function, increased expression of tubular injury biomarkers, and tubular injury evident by histology. Pathways involved in AKI include apoptosis, necrosis, inflammation, and increased oxidative stress, ultimately providing a translational platform for testing the therapeutic efficacy of potential interventions. This review provides a discussion of the foundation laid by cisplatin-induced AKI rodent models for our current understanding of AKI molecular pathophysiology.


Subject(s)
Acute Kidney Injury/chemically induced , Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Animals , Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Disease Models, Animal , Humans , Kidney/drug effects , Kidney/pathology , Kidney/physiopathology , Neoplasms/drug therapy
6.
Am J Physiol Renal Physiol ; 317(1): F187-F196, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31042058

ABSTRACT

Autosomal dominant polycystic kidney disease (PKD) is characterized by cyst formation and growth, which are partially driven by abnormal proliferation of tubular cells. Proproliferative mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2) are activated in the kidneys of mice with PKD. Sirolimus indirectly inhibits mTORC1. Novel mTOR kinase inhibitors directly inhibit mTOR kinase, resulting in the inhibition of mTORC1 and mTORC2. The aim of the present study was to determine the effects of sirolimus versus the mTOR kinase inhibitor torin2 on cyst growth and kidney function in the Pkd1 p.R3277C (Pkd1RC/RC) mouse model, a hypomorphic Pkd1 model orthologous to the human condition, and to determine the effects of sirolimus versus torin2 on mTORC1 and mTORC2 signaling in PKD1-/- cells and in the kidneys of Pkd1RC/RC mice. In vitro, both inhibitors reduced mTORC1 and mTORC2 phosphorylated substrates and negatively impacted cellular metabolic activity, as measured by MTT assay. Pkd1RC/RC mice were treated with sirolimus or torin2 from 50 to 120 days of age. Torin2 was as effective as sirolimus in decreasing cyst growth and improving loss of kidney function. Both sirolimus and torin2 decreased phosphorylated S6 protein, phosphorylated eukaryotic translation initiation factor 4E-binding protein 1, phosphorylated Akt, and proliferation in Pkd1RC/RC kidneys. In conclusion, torin2 and sirolimus were equally effective in decreasing cyst burden and improving kidney function and mediated comparable effects on mTORC1 and mTORC2 signaling and proliferation in the Pkd1RC/RC kidney.


Subject(s)
Kidney Tubules/drug effects , Mutation , Naphthyridines/pharmacology , Polycystic Kidney, Autosomal Dominant/drug therapy , Protein Kinase Inhibitors/pharmacology , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , TRPP Cation Channels/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Apoptosis/drug effects , Cell Cycle Proteins/metabolism , Cell Proliferation/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Humans , Kidney Tubules/enzymology , Kidney Tubules/physiopathology , Male , Mice, Inbred C57BL , Mice, Mutant Strains , Phosphorylation , Polycystic Kidney, Autosomal Dominant/enzymology , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/physiopathology , Proto-Oncogene Proteins c-akt/metabolism , Ribosomal Protein S6 Kinases/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
7.
Pediatr Crit Care Med ; 20(1): 27-37, 2019 01.
Article in English | MEDLINE | ID: mdl-30395106

ABSTRACT

OBJECTIVES: Examine the relationship between perioperative renal regional tissue oximetry, urinary biomarkers, and acute kidney injury in infants after congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, observational. SETTING: Cardiac operating room and cardiac ICU. PATIENTS: Neonates and infants without history of kidney injury or anatomic renal abnormality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Renal regional tissue oximetry was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2 together with insulin-like growth factor-binding protein 7 were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no acute kidney injury, stage 1, or Stage 2-3 acute kidney injury using the Kidney Disease: Improving Global Outcomes criteria with 43 of 70 (61%) meeting criteria for any stage acute kidney injury. Stage 2-3 acute kidney injury patients had higher tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours (0.3 vs 0.14 for stage 1 acute kidney injury and 0.05 for no acute kidney injury; p = 0.052) and 24 hours postoperatively (1.71 vs 0.27 for stage 1 acute kidney injury and 0.19 for no acute kidney injury, p = 0.027) and higher neutrophil gelatinase-associated lipocalin levels at 24 hours postoperatively (10.3 vs 3.4 for stage 1 acute kidney injury and 6.2 for no acute kidney injury, p = 0.019). Stage 2-3 acute kidney injury patients had lower mean cardiac ICU renal regional tissue oximetry (66% vs 79% for stage 1 acute kidney injury and 84% for no acute kidney injury, p = 0.038). Regression analyses showed that tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours postoperatively and nadir intraoperative renal regional tissue oximetry to be independent predictors of postoperative kidney damage as measured by urinary neutrophil gelatinase-associated lipocalin. CONCLUSIONS: We observed modest differences in perioperative renal regional tissue oximetry and urinary biomarker levels compared between acute kidney injury groups classified by creatinine-dependent Kidney Disease: Improving Global Outcomes criteria, but there were significant correlations between renal regional tissue oximetry, tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7, and postoperative neutrophil gelatinase-associated lipocalin levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone, and continuous monitoring of renal regional tissue oximetry may be more sensitive to important subclinical acute kidney injury.


Subject(s)
Acute Kidney Injury/physiopathology , Cardiac Surgical Procedures/adverse effects , Creatinine/blood , Heart Defects, Congenital/surgery , Postoperative Complications/physiopathology , Acute Kidney Injury/etiology , Acute Kidney Injury/urine , Biomarkers , Female , Humans , Infant , Infant, Newborn , Insulin-Like Growth Factor Binding Proteins/urine , Lipocalin-2/urine , Male , Oximetry , Postoperative Complications/epidemiology , Postoperative Complications/urine , Prospective Studies , Severity of Illness Index , Spectroscopy, Near-Infrared , Tissue Inhibitor of Metalloproteinase-2/urine
8.
Paediatr Anaesth ; 26(11): 1060-1063, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27550555

ABSTRACT

AIM: Caudal epidural anesthesia has been shown to reduce stress response and shorten the time to extubation in children after cardiac surgery. Combined with general anesthesia, regional anesthesia has been proven to be safe and efficacious in the pediatric population. It is not known, however, whether the use of caudal anesthesia actually reduces postoperative pain scores and decreases postoperative opioid use. METHODS: We retrospectively analyzed the charts of 199 children who underwent repair for atrial septal defect (ASD), ventricular septal defect (VSD), and Tetralogy of Fallot (TOF) at a major academic children's hospital between 2010 and 2013. RESULTS: Eighty-six patients underwent preoperative placement of caudal anesthesia (bupivacaine 0.25% 1 ml·kg-1 up to 20 ml + clonidine 2mcg·kg-1 + Duramorph 40 mcg·kg-1 up to 2.5 mg) and 113 patients did not have a caudal block. Postoperative cardiac intensive care pain scores were analyzed according to standard nurse-recorded patient-appropriate pain scales ranging from 0 to 10 (CRIES for neonates and FLACC for 2 months-7 years). There was no statistical difference between caudal and noncaudal groups with respect to postoperative pain scores or with postoperative opioid requirements. There was a statistical significance with regard to intraoperative opioid use as noncaudal patients invariably received more opioid during the procedure. CONCLUSION: Although regional anesthesia reduced intraoperative opioid usage, there was no difference in postoperative opioid usage or pain scores.


Subject(s)
Analgesics/administration & dosage , Anesthesia, Caudal/methods , Anesthetics, Local/administration & dosage , Cardiac Surgical Procedures , Heart Defects, Congenital/surgery , Pain, Postoperative/drug therapy , Adolescent , Analgesics, Opioid , Bupivacaine , Child , Child, Preschool , Clonidine , Female , Humans , Infant , Male , Retrospective Studies
9.
Case Rep Anesthesiol ; 2014: 739463, 2014.
Article in English | MEDLINE | ID: mdl-25610661

ABSTRACT

Microstomia is the term used to describe a reduction in the size of the oral aperture that is severe enough to compromise quality of life, nutrition, and cosmesis. Few cases of congenital microstomia have been reported as most microstomia cases are due to burn injuries. We are presenting a case of a neonate who was found to be in respiratory distress with severe congenital microstomia from no known cause. This case illustrates the rarity of this type of pathologic anatomy as well as the teamwork and tools necessary to treat these patients.

SELECTION OF CITATIONS
SEARCH DETAIL
...