Anti-NMDA encephalitis secondary to an ovarian teratoma presenting as altered mental status in a 32-year-old woman: A case report.

NMDA-R encephalitis is an autoimmune encephalitis that is known to be associated with ovarian teratomas. Eighty to 100 % of patients initially present with neuropsychiatric symptoms. Early recognition and intervention are critical to management and prognosis. This case demonstrates non-specific presenting symptoms of NMDA-R encephalitis. A 32-year-old woman presented to the emergency room with headache, nausea, vomiting, and photophobia. She was discharged with probable aseptic meningitis. Eight days later, she represented with delusional thought content, perseverative speech, and bizarre behavior. Cerebrospinal fluid studies showed elevated protein and mild pleocytosis. A computed tomography scan with contrast showed a 35-mm complex cystic lesion in the right adnexa, which was resected. Confirmatory pathology showed a mature cystic teratoma. Paraneoplastic panel later resulted positive for NMDA-R encephalitis. The patient was treated with methylprednisolone, IVIG, plasmapheresis, and rituximab. The clinical course was complicated by a hypersensitivity reaction to rituximab, non-convulsive status epilepticus requiring intubation, dysphagia requiring a PEG placement, a rectal ulcer causing acute blood loss anemia requiring multiple blood transfusions, bilateral hearing loss, and a left lung pneumothorax. The patient's mood, cognition, and motor function were favorably improving 19 months after diagnosis. This case illustrates presenting signs of NMDA-R encephalitis in a young woman as headache and altered mental status followed by psychosis and epilepsy. Treatment should involve a multidisciplinary team and be individualized and escalated in patients with worsening clinical status refractory to first-line therapy. Further research is warranted to understand the optimal treatment strategy for this disease.

Association between Etomidate Use for Rapid Sequence Intubation and Adrenal Insufficiency in Sepsis.

Background The risk of adrenal insufficiency (AI) in using single-dose etomidate for intubation among patients with sepsis remains controversial. Our aim was to assess the prevalence of AI and characterize the risk factors in patients who received etomidate for rapid sequence intubation (RSI). Methods This is a retrospective study of prospectively-acquired data evaluating surgical intensive care unit (SICU) patients who developed respiratory failure undergoing RSI. Results Of the 44 adult SICU patients who developed respiratory failure, 34 patients received etomidate. The average age for the total cohort, for the patients that received etomidate and for those who did not, was 70.91 ± 14.92, 72.82 ± 13.61 years and 64.40 ± 15.93, respectively. Twenty-four patients of the total cohort (54.55%) developed AI; 26 had septic shock (59.09%), and 16 patients had AI and septic shock (36.36%). There was no statistical significance between the incidence of AI in patients who received etomidate (47%) and those who did not (80%). However, in the subset of patients who received etomidate for RSI, there was a non-significant trend toward increased incidence of AI in those who were septic compared to those who were not (p = 0.06). Conclusion A single dose of etomidate used for RSI in SICU patients is not associated with the development of AI or mortality. However, a trend was shown, although not statistically significant, towards the development of AI in septic patients. High-quality and adequately powered randomized control trials (RCTs) are warranted.

Fenoldopam Increases Urine Output in Oliguric Critically Ill Surgical Patients.

Background Fenoldopam is a short-acting dopamine A1 receptor agonist which mediates vasodilation of the renal arteries, thereby increasing urine output. The objective of this study was to compare the effects of fenoldopam and its synergistic effect on furosemide for improving the urine output in postoperative critically ill patients with acute kidney injury (AKI). Methods This is a retrospective study of postoperative critically ill patients with AKI. Patients who received furosemide (control group) were compared with those who received furosemide plus fenoldopam (treatment group) and evaluated at 12 and 24 hours post-treatment. Patients with oliguria and AKI were included in the study, while patients with chronic kidney disease (CKD) were excluded. Glomerular filtration rate, serum creatinine, blood pressure, calculated fluid accumulation, fluid intake, urine output, and total fluid output were used as variables to assess the medication effect. Results Of the 126 patients who met the inclusion and exclusion criteria, 87 patients received furosemide alone, and 39 patients received furosemide plus fenoldopam during their first 24 hours of admission to the surgical intensive care unit (SICU). Although not statistically significant, the addition of fenoldopam demonstrated an increase in mean urine output of 1525ml (IQR; 1530-2095) in the first 24 hours (P=0.06). There was also noted an increase in the urine output (p= 0.07) and a decrease in the total fluid accumulation when fenoldopam was co-administered with furosemide when compared to the patients who were only treated with furosemide (p=0.06). There was no significant change in creatinine clearance from baseline in either group.  Conclusion Fenoldopam may increase urine output in postoperative critically ill patients with acute kidney injury when administered within the first 24 hours of presentation. Based on our results, fenoldopam appears to have a synergistic effect with furosemide in our study population.

Incidence of Sepsis and Mortality With Prior Exposure of HMG-COA Reductase Inhibitors in a Surgical Intensive Care Population.

The anti-inflammatory properties of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may reduce the risk of developing sepsis in surgical intensive care patients and improve outcomes in those who do become septic. The objective of this study was to assess whether surgical intensive care unit (SICU) patients with prior exposure to HMG-CoA reductase inhibitors had a lower incidence of developing sepsis and improved outcomes. A retrospective cohort study was conducted. Patient demographic data, statin use, sequential organ failure assessment (SOFA) scores, vasopressor requirements, ventilator days, length of SICU stay, and mortality in septic patients were collected. Incidence of development of sepsis was determined using systemic inflammatory response syndrome criteria. Patients were grouped into cohorts based on whether they met the sepsis criteria and if they had previously received statins. Cohorts of patients who did and did not become septic with prior statin exposure were compared and an odds ratio was calculated to determine a protective effect. The setting was a SICU. The study comprised of 455 SICU patients and had no interventions. Among the 455 SICU patients, 427 patients were included for the final results. Patients receiving statins verses not receiving statins were similar in demographics. Previous statin exposure had a protective effect in the development of sepsis (9.77% on statins vs. 33.6% without statins; odds ratio 0.203, confidence interval 0.118-0.351). Of those patients who developed sepsis, there was a statistically significant decrease in 28-day mortality in patients with prior statin exposure (P = 0.0341). No statistical difference was noted in length of stay, vasopressor requirements, or days on mechanical ventilation. Prior exposure to statins may have a protective effect on the development of sepsis and decrease mortality in critically ill surgical patients.

Theoretical pharmacokinetic drug alterations in pediatric celiac disease.

INTRODUCTION: The incidence of pediatric celiac disease has risen and many of these children will receive medications at some time in their life. However, the absorption of drugs in pediatric patients with celiac disease has never been studied. The few studies that do exist have only been performed in adults and indicate that drug concentrations can be altered for some drugs. It is also noteworthy that few researchers have conducted studies to determine if the distribution, metabolism, and excretion of drugs are altered in celiac disease. AREAS COVERED: The pharmacokinetics of drugs greatly differ between children and adults. Combined with the pathophysiological changes known to occur with celiac disease, there is compelling evidence to support that drug exposure in pediatric celiac disease may be altered. Relevant characteristics of celiac disease that may affect drug disposition include intestinal atrophy, hypoalbuminemia, reduced CYP3A enzymes, and thyroid dysfunction. EXPERT OPINION: The safety and efficacy of drug dosing in children with celiac disease can be enhanced with additional pharmacokinetic studies of commonly prescribed drugs in this population. Ideally, these studies should include drugs that have high bioavailability, are highly protein bound, undergo extensive CYP3A enzyme metabolism, and/or have a narrow therapeutic range.

Modification of a pharmacokinetics course design to improve student performance.

OBJECTIVE: To determine if the addition of weekly quizzes or reducing the number of faculty members teaching improved third-year (P3) pharmacy students' final grades in a clinical pharmacokinetics course. DESIGN: Four sections of a pharmacokinetics and pharmacodynamics course were divided according to the number of faculty members teaching the course and the administration of weekly quizzes. Two sections were taught by 6 faculty members and 2 were taught by 3 faculty members. Also, 1 section in each group received weekly quizzes, creating a 2-by-2 design. ASSESSMENT: The performance of the 201 P3 students enrolled in the course was assessed by comparing the average of 3 examination grades while excluding quiz grades. The mean final grade of classes in which quizzes were not administered was lower than that for classes in which quizzes were administered (p=0.019). The mean final grade in classes taught by 3 faculty members vs 6 faculty members was higher, but not significantly. A positive significant correlation existed between performance in a prerequisite biopharmaceutics class and this advanced class. CONCLUSION: Making minor modifications to the delivery of a course, such as number of quizzes administered and number of faculty members teaching the course, had a positive impact on student performance. Grades in a prerequisite course may enable earlier identification of students at risk of poor performance in advanced courses.

A quantitative trait locus for ascites on chromosome 9 in broiler chicken lines.

A genome-wide SNP survey was used to identify chromosomal regions that showed linkage disequilibrium with respect to ascites susceptibility and ventricular hypertrophy in an F2 cross between previously described ascites-resistant and -susceptible lines. Variable number tandem repeats were used to obtain genotype data to further characterize these regions. A region on chromosome 9 (12 to 13 Mbp in 2011 assembly) shows association with ascites in the ascites lines and in several commercial broiler breeder lines with a significant sex effect. There are 2 candidate genes, AGTR1 (an angiotensin II type 1 receptor) and UTS2D (urotensin 2 domain containing), in this region that have been associated with hypertension and hypoxic response in mammals.

Prospective randomized controlled trial of The Stabilis Stand Alone Cage (SAC) versus Bagby and Kuslich (BAK) implants for anterior lumbar interbody fusion.

BACKGROUND: Degenerative disc disease is common and debilitating for many patients. If conservative extensive care fails, anterior lumbar interbody fusion has proven to be an alternative form of surgical management. The Stabilis Stand Alone Cage(SAC) was introduced as a method to obtain stability and fusion. The purpose of this study was to determine whether the Stabilis Stand Alone Cage (SAC) is comparable in safety and efficacy to the Bagby and Kuslich (BAK) device. METHODS: As part of a prospective, randomized, controlled FDA trial, 73 patients underwent anterior interbody fusion using either the SAC(56%) or the BAK device (44%). RESULTS: Background characteristics were similar between the two groups. There was no significant difference between the SAC and BAK groups in mean operative time or mean blood loss during surgery. Adverse event rates did not differ between the groups. Assessment of plain radiographs could not confirm solid fusion in 63% of control and 71% of study patients. Functional scores from Owestry and SF-36 improved in both groups by the two-year follow-up. There were no significant differences between the SAC and BAK patients with respect to outcome. CONCLUSIONS: Both the Stabilis Stand Alone Cage and the BAK Cage provided satisfactory improvement in function and pain relief, despite less than expected radiographic fusion rates. The apparent incongruency between fusion rates and functional outcomes suggests that either radiographs underestimate the true incidence of fusion, or that patients are obtaining good pain relief and improved function despite a lower rate of fusion than previously reported. This was a Level III study.

Drug absorption in celiac disease.

PURPOSE: Published evidence on established and theorized effects of celiac disease on drug absorption and pharmacokinetics is reviewed. SUMMARY: Patients with celiac disease develop a variety of gastric disorders requiring oral medications, but the impact of damage to intestinal villi and other celiac disease sequelae on drug absorption remains poorly understood. A review of the pertinent literature (English-language articles on research in adults published during the period 1970-August 2012) identified several reports of altered drug absorption mechanisms in patients with celiac disease, including accelerated or delayed gastric emptying, increased permeability of jejunal mucosa, changes in intraluminal pH, decreased intestinal surface area, and reduced intestinal cytochrome P-450 enzymes. A small number of published studies suggest that celiac disease may be associated with altered drug absorption, resulting in higher serum concentrations of propranolol, lower peak concentrations of acetaminophen and practolol, higher dosing requirements with levothyroxine, impaired or delayed absorption of certain antibiotics, and other pharmacokinetic effects with a potential impact on medication efficacy and toxicity. However, these studies involved very small patient samples and were poorly controlled, with some yielding contradictory results. More and larger pharmacokinetic studies in patients with celiac disease-especially studies of drugs that are dosed empirically or are not amenable to dosage adjustment according to vital signs or laboratory values-are needed. CONCLUSION: Given the sometimes conflicting data on drug absorption in the context of celiac disease, cautious medication selection, dosage adjustment, and monitoring for efficacy and potential adverse effects are advised.

Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica.

OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.

Neuroleptic-induced catatonia in two hospitalized patients.

PURPOSE: To report the cases of 2 hospitalized patients with chronic psychotic disorders who developed neuroleptic-induced catatonia (NIC), a catatonic-extrapyramidal syndrome occurring after administration of a D2-receptor antagonist, and delineate the importance of prompt recognition and treatment. METHODS: Two patients with chronic psychotic disorders were admitted to the hospital for unstable medical conditions at which time their maintenance antipsychotic therapy was discontinued. Following administration of intravenous haloperidol, both patients developed catatonic and extrapyramidal signs. Both patients developed catatonia, rigidity, hyperthermia, leukocytosis, and elevations in creatine kinase. In both cases, the patients met the criteria for catatonia as evidenced by motoric immobility, stupor, mutism, and negativism. The syndrome resolved within a few days of stopping haloperidol and initiation of lorazepam. CONCLUSION: Neuroleptic-induced catatonia is underrecognized and can lead to potentially severe complications, although early recognition and treatment may prevent progression and complications. Previous reports do not underscore the importance of prompt recognition and treatment.

Donepezil dosing strategies: pharmacokinetic considerations.

Donepezil (Aricept) is a cholinesterase inhibitor approved for the treatment of Alzheimer's disease. Immediate release formulations of 5- and 10-mg tablets were approved by the Food and Drug Administration in the United States in 1996. In July 2010, the Food and Drug Administration approved a 23-mg sustained release (SR) formulation. The SR formulation may provide additional benefit to patients receiving 10 mg daily but the incidence of adverse reactions is increased. We derived plasma concentration profiles for higher dose immediate-release formulations (15 mg once daily, 10 mg twice daily, and 20 mg once daily) and for the profile anticipated to result from the 23-mg SR formulation. Our model predicts similar steady-state concentration profiles for 10 mg twice daily, 20 mg once daily, and 23 mg SR once daily. This provides the theoretical basis for incremental immediate release dose escalation to minimize the emergence of adverse reactions and the potential to offer a cost-effective alternative to the SR formulation with currently approved generic immediate release formulations.

Cholinesterase inhibitors: applying pharmacokinetics to clinical decision making.

BACKGROUND: Cholinesterase inhibitors are indicated for the treatment of Alzheimer-type dementia. There are few direct comparative studies of adverse effects or studies to suggest clinical superiority of one inhibitor over the others. OBJECTIVE: The objective of this study was to relate pharmacokinetic differences among the agents to potential clinical considerations. METHODS: Population pharmacokinetics were obtained from US Food and Drug Administration-approved label information and published literature. Plasma concentration-time profiles were derived from these parameters using noncompartmental pharmacokinetic modeling. RESULTS: Plasma concentration profiles differed significantly among different agents and between different formulations of the same agent. CONCLUSIONS: The initial choice among the various cholinesterase inhibitors requires consideration to adherence and cost. Consideration to differences in pharmacokinetics among these drugs provides a better understanding for the clinical practice of dose titration, identification and management of drug-related side effects, and lapses in therapy. Pharmacokinetic considerations among the various agents and formulations provide the clinician with options to enhance therapy when these agents are chosen for treatment of patients with Alzheimer-type dementia.

Transpedicular aspiration of osteoprogenitor cells from the vertebral body: progenitor cell concentrations affected by serial aspiration.

BACKGROUND CONTEXT: Spinal fusion is facilitated when the fusion site is augmented with autograft bone. Iliac crest, long the preferred source of autograft material, is the site of frequent complications and pain. Connective tissue progenitor cells (CTPs) aspirated from marrow provide a promising alternative to traditional autograft harvest. The vertebral body represents an even larger potential reservoir of progenitor cells than the ilium. PURPOSE: To test the hypothesis that a suitable concentration of osteoprogenitor cells can be aspirated from different depths of the vertebral body, maintaining progenitor cell concentrations comparable to the "gold standard," the iliac crest, even after sequential aspirations along the same transpedicular axis. STUDY DESIGN: Prospective clinical investigation quantifying CTP concentrations within the vertebral body relative to depth of sequential aspirations. PATIENT SAMPLE: Adult men and women undergoing elective posterior lumbar fusion and pedicle screw instrumentation (six men and seven women, mean age 56 years [range 40-74 years]). OUTCOME MEASURES: Cell count, CTP concentration (CTPs/cc marrow), and CTP prevalence (CTPs/million cells) were calculated for both individual and pooled aspirate samples. METHODS: Thirteen patients were enrolled into an institutional review board-approved protocol studying transpedicular aspiration of marrow progenitor cells. Connective tissue progenitor cells were aspirated from four depths along the transpedicular axis of the vertebral body and quantified according to cell concentration and CTP prevalence. Histochemical analysis of alkaline phosphatase-positive colony-forming units (CFUs) provided the prevalence of vertebral CTPs relative to depth of aspiration, vertebral level, age, and gender. RESULTS: Four 2.0cc aspirations were obtained from each pedicle of lumbar vertebrae selected for pedicle screw fixation (four 2.0cc aspirates from each of four pedicles). Aspirates of vertebral marrow demonstrated comparable or greater concentrations of CFUs compared with standards previously established for the iliac crest. Overall, the 208 aspirations from 26 vertebral bodies provided a mean CTP concentration of 741.5+/-976.2 CTPs per cubic centimeter of marrow, ranging from a mean concentration of 1316+/-1473 CTPs per cubic centimeter of marrow at superficial (30mm) aspirations to 439+/-557 CTPs per cubic centimeter marrow at deepest (45mm) aspiration depths (p<.00002). There were no significant differences relative to vertebral body level, side aspirated, or gender. An age-related decline in cellularity was suggested for vertebral body aspirates. CONCLUSIONS: The vertebral body is a potential marrow reservoir for aspiration of autograft osteogenic CTPs that can be used to augment spinal fusion. The cancellous bone within that portion of the vertebral body routinely cannulated during pedicle screw placement allows serial aspirations with only modest depletion of progenitor cell concentrations or dilution with peripheral blood. Connective tissue progenitor cell concentrations from all depths were comparable to the mean levels previously established for the iliac crest. The ability to simultaneously harvest progenitor cells for graft augmentation while preparing the pilot hole for pedicle screw fixation will expand the potential for cell harvest techniques for fusion augmentation and reduce the need for iliac crest harvest.