Ochsner Baptist Medical Center

For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

Conditions with limb pterygia and congenital contractures were reviewed as part of a study of over 350 infants with arthrogryposis. Emphasis was placed on inheritance and variability of distinct pterygium conditions. Eleven patients with limb pterygia were recognized in our study and are described here. Seven of the 350 patients with congenital contractures had the autosomal recessively inherited multiple pterygium syndrome (Patients 1-7). Three of the seven are sibs, a fourth was born to consanguineous parents, and three were chance isolated cases. These seven had multiple joint webs, unusual finger contractures, syndactyly, rocker bottom feet, ptosis, antimongoloid slant of palpebral fissures, epicanthal folds, highly arched palate, scoliosis, and short stature. There is intrafamilial variability. Three patients from one family had a lethal multiple pterygium syndrome. Two were monozygotic twins. They had webbing and contractures of the elbows, knees, neck, and fingers, calcaneovalgus deformity of the feet, and an unusual facial appearance: hypertelorism, flat nose, antimongoloid slant of palpebral fissures, apparently low-set ears. One had a cleft palate. Internal malformations included: bilateral pulmonary hypoplasia, small heart, absence of the appendix, and attenuation of the ascending and transverse colon. One sporadic case of lethal popliteal pterygium with facial clefts was studied. Multiple anomalies included: ankyloblepharon filiforme adnatum, upslanting palpebral fissures, hypoplasia of nasal cartilages, frenula, clefts into the oropharynx lateral to the mouth, apparently low-set ears with slit-like canals, large popliteal pterygia, syndactyly with fusion of all digits in hands and feet, and hypoplastic labia.

BACKGROUND: Gradually progressive development of complete heart block in young people often is associated with cardiac arrhythmia and sudden death, but the pathogenesis remains unexplained. METHODS AND RESULTS: A young woman with complete heart block died suddenly. Her mother had serological but no clinical evidence of antiphospholipid syndrome. Five brothers of another family had arrhythmia and heart block. Three died suddenly; the other two have automatic defibrillators and are alive. The hearts from the young woman and two of the three brothers who died were available for our histological examination of their cardiac conduction systems. In two of the three hearts, the AV node was absent; in the third heart, only fragments of the AV node remained. In all three hearts, the sinus node was nearly destroyed by a noninflammatory degeneration with no abnormal fibrosis or infiltrate. In each heart, the interatrial and internodal pathways were similarly involved, and in the young woman, there were no myocardial cells in which these pathways normally exist. CONCLUSIONS: In these three subjects with progressive development of complete heart block and various arrhythmias, all of whom died suddenly, the histological abnormalities of their cardiac conduction systems are best interpreted as resulting from apoptosis. Programmed cell death is a logical explanation for the pathogenesis of this puzzling clinical picture.

Exosomes are membrane-bound nanovesicles that transport molecular signals between cells. This study determined changes in maternal plasma exosome proteomics contents in term and preterm births. Maternal plasma (MP) samples were collected from group 1: term not in labor (TNIL, n = 13); group 2: term in labor (TL, n = 11); group 3: preterm premature rupture of membranes (pPROM, n = 8); and group 4: preterm birth (PTB, n = 13). Exosomes isolated from plasma by differential density centrifugation followed by size exclusion chromatography were characterized by morphology (electron microscopy), quantity and size (nanoparticle tracking analysis), and markers (western blot). A quantitative, information-independent acquisition [sequential windowed acquisition of all theoretical mass spectra (SWATH-MS)] approach was used to determine the protein profile in exosomes. Ingenuity Pathway Analysis determined pathways associated with the protein profile identified in exosomes. MP exosomes were spherical, had a mean diameter of 120 nm, and were positive for exosomal proteins CD63 and TSG101 irrespective of pregnancy status. No distinct changes in exosome quantities were seen in maternal circulation across the groups. SWATH-MS identified 72 statistically significant proteins across the groups studied. Bioinformatics analysis showed the proteins within the exosomes in TNIL, TL, pPROM, and PTB target pathways mainly associated with inflammatory and metabolic signals. Exosomal data suggest that homeostatic imbalances, specifically inflammatory and endocrine signaling, might disrupt pregnancy maintenance resulting in labor-related changes both at term and preterm. Reflection of physiologic changes in exosomes is suggestive of its usefulness as biomarkers and cellular function indicators.

BACKGROUND: Therapeutic approaches to addressing insufficient lactation are available but remain poorly understood. Current trends in maternal health, such as increasing rates of obesity, delayed age at childbearing, and high rates of cesarean section, may be associated with physiological challenges for lactation that cannot be managed by counseling alone. Women who have not had success with counseling alone, including adoptive mothers seeking to induce lactation, may use galactagogues (pharmaceutical and herbal compounds used to increase lactation). We present a review of selected studies of galactagogues and data indicating popular demand for such products. METHODS: A systematic search was conducted for published studies on the use of galactagogues for breast-feeding. The following databases were searched: MEDLINE (PubMed), EBSCO (Academic Search Complete), and EMBASE. The search was conducted between July 15, 2015, and August 18, 2015; only English language articles were included, and we imposed no restrictions on publication date. Two authors independently reviewed the studies and extracted data. RESULTS: Blinded, placebo-controlled clinical trials of 2 pharmaceutical galactagogues (domperidone and metoclopramide) and 5 popular herbal galactagogues (shatavari, fenugreek, silymarin, garlic, and malunggay) were identified. All of the studies identified for domperidone showed a significant difference in milk production between the treatment and placebo groups. Of the 6 trials of metoclopramide, only 1 study showed a significant difference in milk production compared to placebo. Results of the clinical trials on herbal galactagogues were mixed. Our review of the evidence for the efficacy of popular pharmaceutical and herbal galactagogues revealed a dearth of high-quality clinical trials and mixed results. CONCLUSION: Health providers face the challenge of prescribing or recommending galactagogues without the benefit of robust evidence. Given the suboptimal rates of exclusive breast-feeding worldwide and the availability and demand for medical and herbal lactation therapies, controlled trials and analyses investigating these medicines are urgently warranted.

BACKGROUND: The flipped classroom is a student-centered approach to learning that increases active learning for the student compared to traditional classroom-based instruction. In the flipped classroom model, students are first exposed to the learning material through didactics outside of the classroom, usually in the form of written material, voice-over lectures, or videos. During the formal teaching time, an instructor facilitates student-driven discussion of the material via case scenarios, allowing for complex problem solving, peer interaction, and a deep understanding of the concepts. A successful flipped classroom should have three goals: (1) allow the students to become critical thinkers, (2) fully engage students and instructors, and (3) stimulate the development of a deep understanding of the material. The flipped classroom model includes teaching and learning methods that can appeal to all four generations in the academic environment. METHODS: During the 2015 academic year, we implemented the flipped classroom in the obstetrics and gynecology clerkship for the Ochsner Clinical School in New Orleans, LA. Voice-over presentations of the lectures that had been given to students in prior years were recorded and made available to the students through an online classroom. Weekly problem-based learning sessions matched to the subjects of the traditional lectures were held, and the faculty who had previously presented the information in the traditional lecture format facilitated the problem-based learning sessions. The knowledge base of students was evaluated at the end of the rotation via a multiple-choice question examination and the Objective Structured Clinical Examination (OSCE) as had been done in previous years. We compared demographic information and examination scores for traditional teaching and flipped classroom groups of students. The traditional teaching group consisted of students from Rotation 2 and Rotation 3 of the 2014 academic year who received traditional classroom-based instruction. The flipped classroom group consisted of students from Rotation 2 and Rotation 3 of the 2015 academic year who received formal didactics via voice-over presentation and had the weekly problem-based learning sessions. RESULTS: When comparing the students taught by traditional methods to those taught in the flipped classroom model, we saw a statistically significant increase in test scores on the multiple-choice question examination in both the obstetrics and gynecology sections in Rotation 2. While the average score for the flipped classroom group increased in Rotation 3 on the obstetrics section of the multiple-choice question examination, the difference was not statistically significant. Unexpectedly, the average score on the gynecology portion of the multiple-choice question examination decreased among the flipped classroom group compared to the traditional teaching group, and this decrease was statistically significant. For both the obstetrics and the gynecology portions of the OSCE, we saw statistically significant increases in the scores for the flipped classroom group in both Rotation 2 and Rotation 3 compared to the traditional teaching group. With the exception of the gynecology portion of the multiple-choice question examination in Rotation 3, we saw improvement in scores after the implementation of the flipped classroom. CONCLUSION: The flipped classroom is a feasible and useful alternative to the traditional classroom. It is a method that embraces Generation Y's need for active learning in a group setting while maintaining a traditional classroom method for introducing the information. Active learning increases student engagement and can lead to improved retention of material as demonstrated on standard examinations.

This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

// Zarin Nuzhat 1 , Vyjayanthi Kinhal 1 , Shayna Sharma 1 , Gregory E. Rice 1,2 , Virendra Joshi 3 and Carlos Salomon 1,2 1 Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women&rsquo;s Hospital, The University of Queensland, Brisbane QLD 4029, Australia 2 Department of Obstetrics and Gynecology, Ochsner Baptist Hospital, New Orleans, Louisiana, USA 3 Ochsner Clinic Foundation, New Orleans, Louisiana, USA Correspondence to: Carlos Salomon, email: // Keywords : exosomes, pancreatic cancer, biomarkers Received : August 19, 2016 Accepted : December 13, 2016 Published : December 16, 2016 Abstract Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a &lsquo;fingerprint&rsquo; of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.

// Shayna Sharma 1 , Felipe Zu&ntilde;iga 2 , Gregory E. Rice 1, 3 , Lewis C. Perrin 4, 5, 6 , John D. Hooper 5, 6 and Carlos Salomon 1, 2, 3, 5 1 Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women&rsquo;s Hospital, Faculty of Medicine + Biomedical Sciences, The University of Queensland, Brisbane, Australia 2 Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepci&oacute;n, Concepci&oacute;n, Chile 3 Department of Obstetrics and Gynecology, Ochsner Baptist Hospital, New Orleans, Louisiana, USA 4 Mater Health Services, South Brisbane, Australia 5 Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, Australia 6 Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, Australia Correspondence to: Carlos Salomon, email: c.salomongallo@uq.edu.au Keywords: ovarian cancer; exosomes; biomarkers; early detection Received: June 16, 2017&emsp;&emsp;&emsp;&emsp; Accepted: September 08, 2017&emsp;&emsp;&emsp;&emsp; Published: October 31, 2017 ABSTRACT Ovarian cancer usually has a poor prognosis because it predominantly presents as high stage disease. New approaches are required to develop more effective early detection strategies and real-time treatment response monitoring. Nano-sized extracellular vesicles (EVs, including exosomes) may provide an approach to enrich tumor biomarker detection and address this clinical need. Exosomes are membranous extracellular vesicles of approximately 100 nm in diameter that have potential to be used as biomarkers and therapeutic delivery tools for ovarian cancer. Exosomal content (proteins and miRNA) is often parent cell specific thus providing an insight or &ldquo;fingerprint&rdquo; of the intracellular environment. Furthermore, exosomes can aid cell-cell communication and have the ability to modify target cells by transferring their content. Additionally, via the capacity to evade the immune system and remain stable over long periods in circulation, exosomes have potential as natural drug agents. This review examines the potential role of exosomes in diagnosis, drug delivery and real-time monitoring in ovarian cancer.

BACKGROUND: The persistence of syphilis and other bacterial sexually transmitted diseases (STDs) in many areas of the United States suggests that innovative approaches to controlling these diseases are needed. GOAL: To evaluate the feasibility, acceptability, and yield of mobile community-based STD screening and treatment services in high STD incidence areas. STUDY DESIGN: Free, voluntary, confidential screening and treatment for STDs were conducted in high STD incidence neighborhoods of Baton Rouge, Louisiana, using a 32-foot mobile van. Demographic and behavioral data were obtained from participants. Participants were screened for syphilis, chlamydia, and gonorrhea and were also offered HIV testing. Community attitudes toward the screening program were assessed with street-intercept surveys conducted two weeks after screening events. RESULTS: From March 1997 to August 2000, 256 community-based screening events were held. During this period, 3110 blood samples were collected for syphilis testing, of which 37 (1.2%) new cases of syphilis were identified. Of the 2807 blood samples collected for HIV testing, 70 (2.5%) were positive. Of 2229 urine samples, 185 (8.3%) tested positive for Chlamydia trachomatis and 108 (4.9%) positive for Neisseria gonorrhoeae. Of 389 street-intercept surveys, 97% of respondents thought that neighborhood STD testing was a "good" or "very good" idea. CONCLUSION: Mobile community-based STD screening and treatment are feasible, identify high positivity of STDs, and are accepted by the community as an innovative approach to STD control.

NANCE, FRANCIS C. M.D.; DELOACH, DONALD H. M.D.; WELSH, RONALD A. M.D.; BECKER, WALTER F. M.D. Author Information

Carbamazepine is a widely prescribed antiepileptic drug. Owing to the lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100-mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with liquid chromatography-mass spectrometry, and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (l/hr/kg) was significantly lower in men (0.039 ± 0.017) than in women (0.049 ± 0.018; P = 0.007) and in African Americans (0.039 ± 0.017) when compared with Caucasians (0.048 ± 0.018; P = 0.019). Half-life was significantly longer in men than in women as well as in African Americans as compared with Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response.

Pelvic inflammatory disease associated with pregnancy is not commonly reported. We present three illustrative cases at ten, 13, and 26 weeks of gestation. Unlike pelvic abscess, which may be discovered at any stage of gestation, acute salpingitis during pregnancy occurs more commonly in the first trimester. Both processes are associated with substantial fetal wastage. Diagnosis may be difficult if the obstetrician is not aware that these infections can occur during pregnancy. The diagnosis is often made at laparotomy by a physician expecting appendicitis or another inflammatory condition. Since salpingitis during pregnancy, like salpingitis generally, is amenable to antibiotic therapy, surgery may be avoided if appropriate antibiotic therapy is quickly instituted. The pregnant patient and her fetus may be spared general anesthesia and the attendant risks of abdominal surgery.

Colloid osmotic pressure (COP) is an important regulator of fluid movement and can now be measured simply and reliably. The authors used the 4100 Wescor Colloid Osmometer to define COP values and its relation to total protein concentration (TP) in different groups of newborns. The mean COP was 19.4 +/- 2.2 (SD) torr in 99 term infants delivered vaginally and 16.0 +/- 2.1 in 40 term infants delivered by cesarean section (p less than 0.005). The COP was lower in those born operatively without preceding labor (14.9 +/- 1.8). COP correlated well with TP (r = 0.92) in term infants. In 60 sick preterm infants with 362 determinations, COP (12.5 +/- 2.5) was different from term infants (p less than 0.001) and the correlation with TP was poor (r = 0.64). Different therapeutic modalities were found to affect COP widely. Crystalloid infusion decreased COP by 22% and surgery by 32%. The authors conclude that COP varies not only with gestational age but also with mode of delivery and experience of labor. In critically ill preterm neonates, because estimations form TP are inadequate, the only way to obtain a quantitative measure of COP is by direct measurement. Repeated measurements of COP will permit precise selection of the fluids and will warn of changes that may lead to pulmonary edema.

Salivary small extracellular vesicles (sEV) are emerging as a potential liquid biopsy for oral diseases. However, technical difficulties for salivary sEV isolation remain a challenge. Twelve participants (five periodontally healthy, seven gingivitis patients) were recruited and salivary sEV were isolated by ultracentrifuge (UC-sEV) and size exclusion chromatography (SEC-sEV). The effect of UC and SEC on sEV yield, DNA methylation of five cytokine gene promoters (interleukin (IL)−6, tumor necrosis factor (TNF)-α, IL−1β, IL−8, and IL−10), and functional uptake by human primary gingival fibroblasts (hGFs) was investigated. The results demonstrated that SEC-sEV had a higher yield of particles and particle/protein ratios compared to UC-sEV, with a minimal effect on the detection of DNA methylation of five cytokine genes and functional uptake in hGFs (n = 3). Comparing salivary sEV characteristics between gingivitis and healthy patients, gingivitis-UC-sEV were increased compared to the healthy group; while no differences were found in sEV size, oral bacterial gDNA, and DNA methylation for five cytokine gene promoters, for both UC-sEV and SEC-sEV. Overall, the data indicate that SEC results in a higher yield of salivary sEV, with no significant differences in sEV DNA epigenetics, compared to UC.

PURPOSE: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new-onset epilepsy. METHODS: Randomized, double-blind, 28-day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new-onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. RESULTS: At day 28, the estimated seizure-free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment-related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). CONCLUSION: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new-onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new-onset epilepsy requiring rapid treatment initiation.

One hundred forty-six units of two to five-day-old refrigerated blood were washed with the IBM Blood Cell Processor. The ABO and Rh types of the units varied according to available inventory. This study was designed to select the best protocol from the 42 possible combinations utilizing the machine's variable red blood cell override (RCO). A one liter wash program was used. The two parameters selected for study were the per cent red blood cell recovery and the per cent white blood cell removal. The protocol of choice uses a RCO of four seconds in the first and second steps of the program. This protocol yields a washed unit with a mean red blood cell recovery of 82 per cent and a mean white cell removal of 93 per cent. Our studies indicate that the IBM Blood Cell Processor can be used to wash two to five day old refrigerated blood for the preparation of leukocyte-poor blood that would meet the Standards of the AABB.

A classic 2-period crossover bioavailability study was conducted to evaluate the relative and absolute bioavailability of immediate-release (IR) and extended-release (XR) lamotrigine formulations under steady-state conditions in elderly patients with epilepsy. On treatment days, each subject's morning dose (IR or XR lamotrigine) was replaced with an intravenous 50-mg dose of stable-labeled lamotrigine. Lamotrigine concentrations were measured at 13 points between 0 and 96 hours. XR and IR lamotrigine formulations were similar with respect to steady-state area under the concentration-time curve from 0 to 24 hours (AUC0-24 h ss), average concentration (Cavg, ss), and trough concentration (Cτ, ss). A 33% lower fluctuation in concentrations with XR was observed relative to IR lamotrigine. The time to peak concentration (Tmax, ss) was delayed for XR lamotrigine (3.0 vs 1.3 hours) with lower peak concentration (15% lower). The absolute bioavailability for IR and XR formulations was 73% and 92%, respectively. The formulations were bioequivalent with respect to AUC0-24 h ss, Cτ, ss, and Cavg, ss indicating that it may be possible to switch directly from IR to XR lamotrigine without changes in the total daily dose.

PURPOSE: Phentermine is the most prescribed antiobesity drug in America, with 2.43 million prescriptions written in 2011. Case reports suggest there are anesthetic risks, such as refractory hypotension, involved with its perioperative use. Despite these risks and the frequency of phentermine use among plastic surgery patients, there are no published guidelines for the perioperative management of phentermine use in the plastic surgery literature. To address this patient safety issue, we performed a systematic review and provide management recommendations. METHODS: A systematic review of the pharmacology of phentermine and the anesthetic risks involved with its perioperative use was undertaken using the search engines PubMed/MEDLINE, EMBASE, and Scopus. RESULTS: A total of 251 citations were reviewed, yielding 4 articles that discussed perioperative phentermine use and complications with anesthesia. One was a review article, 2 were case reports, and 1 was a letter. Complications included hypotension, hypertension, hypoglycemia, hyperthermia, bradycardia, cardiac depression, and acute pulmonary edema. CONCLUSIONS: The relationship between phentermine and anesthesia, if any, is unclear. Hypotension on induction of general anesthesia is the most reported complication of perioperative phentermine use. Specifically, phentermine-induced hypotension may be unresponsive to vasopressors that rely on catecholamine release, such as ephedrine. Therefore, the decision to perform surgery, especially elective surgery, in a patient taking phentermine should be made with caution. Because of the half-life of phentermine, we recommend discontinuing phentermine for at least 4 days prior to surgery. This differs from the classic 2-week discontinuation period recommended for "fen-phen." The patient should be made aware of the increased risk of surgery, and a skilled anesthesiologist should monitor intraoperative blood pressure and body temperature for signs of autonomic derailment.