Biomedical subjects

Joshua Samuels

Publications and source records attributed to Joshua Samuels.

5 recordsLinked to original sources

PubMed2006

Acute amphotericin B overdose.

OBJECTIVE: To report the clinical course of a woman with cryptococcal meningitis and no previous cardiac disease who developed a fatal cardiac arrhythmia after an acute overdose of amphotericin B and to review its toxicity. CASE SUMMARY: A 41-year-old woman with a history of proliferative glomerulonephritis from systemic lupus erythematosus was admitted with a diagnosis of cryptococcal meningitis. Liposomal amphotericin B was prescribed at the standard dose of 5 mg/kg/day; however, amphotericin B deoxycholate 5 mg/kg was inadvertently administered (usual dose of the deoxycholate formulation is 0.5-0.8 mg/kg/day). The patient developed cardiac arrhythmias, acute renal failure, and anemia. The medication error was noticed after she had received 2 doses of amphotericin B deoxycholate, and it was then discontinued. Despite treatment in the intensive care unit, the woman died on the sixth day after admission. DISCUSSION: Amphotericin B deoxycholate has been reported to produce significant cardiac toxicity, with ventricular arrhythmias and bradycardia reported in overdoses in children and in adults with preexisting cardiac disease, even when administered in conventional dosages and infusion rates. Use of the Naranjo probability scale indicated a highly probable relationship between the observed cardiac toxicity and amphotericin B deoxycholate therapy in this patient. CONCLUSIONS: Given the fulminant course of amphotericin B deoxycholate overdosage and lack of effective therapy, stringent safeguards against its improper administration should be in place.

Acute Disease↗

PubMed2006

Fenoldopam improves corticomedullary oxygen delivery and attenuates angiogenesis gene expression in acute ischemic renal injury.

BACKGROUND/AIMS: Vasoactive compounds are known to affect intrarenal hemodynamics and gene transcription, but specific effects of fenoldopam in the setting of acute renal ischemia are not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam improves corticomedullary tissue oxygen tension (PtO2) and attenuates angiogenesis gene expression in acute renal ischemia. METHODS: Rats anesthetized with 50 mg/kg urethane were divided into 4 groups (n = 6 each): (1) sham with infusion of 0.9% saline; (2) sham with infusion of 0.1 microg x kg(-1) x min(-1) fenoldopam; (3) unilateral renal ischemia followed by 6 h of reperfusion with saline, and (4) ischemia/reperfusion with fenoldopam. Renal artery blood flow (RBF), renal cortical perfusion (RCP), and PtO2 were recorded throughout. Total RNA from left kidneys was used to probe microarrays. Gene expression was measured as percent positive control (GAPDH) and confirmed using RT-PCR. RESULTS: Fenoldopam significantly increased RBF (p < 0.05), RCP (p < 0.01) and PtO2 (p <0.01) in both non-ischemic and post-ischemic kidneys. Fenoldopam attenuated 11 of the 13 ischemia-induced genes and 44 of 78 ischemia-suppressed genes. This attenuation was statistically significant (p < 0.05) for five genes. CONCLUSION: Data from this rat model of ischemic nephropathy suggest that fenoldopam improves intrarenal hemodynamics and attenuates ischemia-related changes in angiogenesis gene expression.

Acute Disease↗

PubMed2006

Improved postoperative outcomes associated with preoperative statin therapy.

Statin therapy is well established for prevention of cardiovascular disease. Statins may also reduce postoperative mortality and morbidity via a pleiotropic (non-lipid-lowering) effect. The authors conducted a meta-analysis to determine the influence of statin treatment on adverse postoperative outcomes in patients undergoing cardiac, vascular, or noncardiovascular surgery. Two independent authors abstracted data from 12 retrospective and 3 prospective trials (n = 223,010 patients). A meta-analysis was performed to evaluate the overall effect of preoperative statin therapy on postoperative outcomes. Preoperative statin therapy was associated with 38% and 59% reduction in the risk of mortality after cardiac (1.9% vs. 3.1%; P = 0.0001) and vascular (1.7% vs. 6.1%; P = 0.0001) surgery, respectively. When including noncardiac surgery, a 44% reduction in mortality (2.2% vs. 3.2%; P = 0.0001) was observed. Preoperative statin therapy may reduce postoperative mortality in patients undergoing surgical procedures. However, the statin associated effects on postoperative cardiovascular morbidity are too variable to draw any conclusion.

Animals↗

PubMed2005

Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Acute tubular necrosis (ATN) occurs commonly in critically ill patients and is associated with increased morbidity and mortality. Fenoldopam is a dopamine receptor alpha1-specific agonist that increases renal blood flow in patients with kidney failure. We hypothesized that administration of low-dose fenoldopam during early ATN would decrease the need for dialysis therapy and/or incidence of death at 21 days. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in 155 patients with early ATN. Patients were considered eligible for enrollment if serum creatinine level increased to 50% greater than admission levels within 24 hours and mean arterial pressure was greater than 70 mm Hg. Patients were randomly assigned to the administration of placebo or fenoldopam for 72 hours. RESULTS: Overall, 22 of 80 patients (27.5%) in the fenoldopam group reached the primary end point compared with 29 of 75 patients (38.7%) in the placebo group (P = 0.235). This 11% absolute reduction in the primary end point was not statistically significant (P = 0.23). Similarly, there was no difference in the incidence of dialysis therapy between patients randomly assigned to fenoldopam (13 of 80 patients; 16.25%) versus the placebo group (19 of 75 patients; 25.3%; P = 0.163). Moreover, there was no statistically significant difference in 21-day mortality rates between the 2 groups (fenoldopam, 13.8% versus placebo, 25.3%; P = 0.068). In secondary analyses, fenoldopam tended to reduce the primary end point in patients without diabetes and postoperative cardiothoracic surgery patients with early ATN (fenoldopam patients without diabetes, 14 of 54 patients [25.9%] versus placebo patients without diabetes, 23 of 52 patients [44.2%]; P = 0.048) and postoperative cardiothoracic patients (6 of 34 patients [17.6%] versus 14 of 36 patients [38.8%]; P = 0.049). Conversely, fenoldopam did not improve the primary end point in patients with diabetes or those with acute renal failure from other causes. A larger multicenter trial using separate randomizations for patients with and without diabetes will be needed to determine the efficacy of fenoldopam mesylate in specific subpopulations with ATN. CONCLUSION: Fenoldopam does not reduce the incidence of death or dialysis therapy in intensive care unit patients with early ATN.

Creatinine↗

PubMed2005

Effect of fenoldopam mesylate in critically ill patients at risk for acute renal failure is dose dependent.

BACKGROUND: Acute renal failure (ARF) is common and difficult to prevent, especially in intensive care unit (ICU) patients with cancer. Therapeutic trials with various agents have generally been ineffective in preventing ARF. We describe the effects of two different doses of the dopamine DA-1 receptor agonist fenoldopam mesylate on renal function in a series of critically ill cancer patients at risk of developing ARF. METHODS: We performed a retrospective chart review of 100 consecutive patients who received fenoldopam mesylate for at least 72 h in the medical and surgical ICUs of The University of Texas M. D. Anderson Cancer Center who were at risk of developing ARF. Eighteen patients received low-dose fenoldopam mesylate (< or =0.05 microg/kg/min). The remaining 82 patients received high-dose fenoldopam mesylate (0.07-0.1 microg/kg/min). Data were collected relating to drug dosage, patient demographics, severity of illness, and indices of renal function. RESULTS: Patients were moderately ill, with a mean APACHE II score of 18+/-6 at initiation of fenoldopam infusion. Eighty-five percent of patients had at least two risk factors for the development of ARF, and 20% had four. For the group overall, the incidence of ARF was 13%, and the hospital mortality rate was 37%. When compared with the low-dose group, patients who received high-dose fenoldopam had a significantly shorter ICU length of stay despite a significantly higher APACHE II score (p=0.01). The high-dose group also had a highly significant decrease in serum creatinine levels at 72 h (p=0.005). CONCLUSIONS: These data support the hypothesis that fenoldopam mesylate may provide a degree of dose-dependent renal protection in cancer patients with early acute renal failure.

Acute Kidney Injury↗