Acute hematological and mood perception effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine: A placebo-controlled, double-blind study.

The purpose of this study was to examine acute hematological and mood perception responses to supplementation with p-synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects visited the laboratory on 6 occasions and were given (in randomized double-blind manner) 103-mg p-synephrine (S), 233-mg caffeine + 104-mg p-synephrine, 240-mg caffeine, 337-mg caffeine + 46-mg p-synephrine, 325-mg caffeine, or a placebo (PL). The subjects sat quietly for 3 hr while completing mood state questionnaires every 30 min. Venous blood samples were collected at baseline (pre) and 3 hr (post) to determine immune, lipid, and chemistry panels. Compared with PL, no significant supplement differences were observed during the S trial with the exception of differential time effects seen in hematocrit (decrease in PL, no change in S), triglycerides and very low-density lipoproteins (no changes in PL, significant decreases in S), and iron (no change in PL, significant elevation in S). Supplements containing caffeine showed increased feelings of attention, excitement, energy, and vigor. These data indicate that consumption of 103-mg p-synephrine does not negatively impact acute blood parameters, does not augment the effects of caffeine, or produce stimulant-like perceptual mood effects.

Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study.

The purpose was to examine cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects were given (in double-blind manner) either 103 mg of p-synephrine (S), 233 mg of caffeine +104 mg of p-synephrine (LC + S), 240 mg of caffeine (LC), 337 mg of caffeine +46 mg of p-synephrine (HC + S), 325 mg of caffeine (HC), or a placebo. The subjects sat quietly for 3 hr while heart rate (HR) and blood pressure were measured. Only HC + S and HC significantly increased mean systolic blood pressure (SBP) during the second hour and tended to increase mean SBP during the third hour. Mean diastolic blood pressure in S was significantly lower than the other trials during the first and second hours, and mean arterial pressure was significantly lower in S compared to the LC, LC + S, HC, and HC + S trials. No differences were observed in HR. Consumption of p-synephrine may acutely reduce diastolic blood pressure and mean arterial pressure and not affect SBP or HR during quiet sitting. The addition of p-synephrine to caffeine did not augment SBP or HR indicating that consumption of up to 104 mg of p-synephrine does not induce cardiovascular stress during quiet sitting.

Transarterial treatment of colorectal cancer liver metastases with irinotecan-loaded drug-eluting beads: technical recommendations.

Transcatheter hepatic arterial administration of irinotecan-loaded drug-eluting beads (DEBIRI) is used to treat liver-only or liver-dominant metastatic disease from colorectal cancer (CRC). Eligibility for DEBIRI should be established in each individual patient by a multidisciplinary team based on comprehensive clinical, imaging, and laboratory assessment. Standardization of DEBIRI technique and protocols would be expected to lead to improved efficacy and safety. The present article provides a set of technical recommendations for the use of DEBIRI in the treatment of hepatic CRC metastases.

Segmental and lobar administration of drug-eluting beads delivering irinotecan leads to tumour destruction: a case-control series.

BACKGROUND: Irinotecan-loaded drug-eluting beads represent a novel drug delivery method that allows for the locoregional delivery of irinotecan to colorectal liver metastases (CRLM). The method has shown impressive response rates. However, the pathological response to this treatment has not previously been demonstrated. METHODS: Patients with easily resectable CRLM were treated with drug-eluting beads delivering irinotecan (DEBIRI) 4 weeks prior to resection. Pathological tumour response was graded using a validated system. The intraoperative detection of previously unidentified disease allowed for the assessment of pathological responses directly attributable to bead treatment. RESULTS: In Patient 1, segmental embolization of the target lesion in segment VIII resulted in 100% necrosis (0% viability). An untreated lesion in segment IV was found to be 30% viable. In Patient 2, subsegmental embolization of the target lesion in segment VI resulted in 60% necrosis and 40% fibrosis (0% viability). An untreated lesion in segment VI remained 60% viable. In Patient 3, lobar embolization of the target lesion in segment II resulted in 0% viability. Two further lesions within the treated hemiliver, both with 0% viability, and one lesion in the untreated hemiliver with 45% viability were discovered at laparotomy. CONCLUSIONS: This series demonstrates the effectiveness of DEBIRI in the treatment of CRLM. High rates of tumour destruction are possible, even with the proximal lobar administration of DEBIRI. Lobar administration appears to be an appropriate method of delivery for integration into future therapeutic regimens.

Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations.

Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.

Blood and body fluid exposures among US medical students in Botswana.

INTRODUCTION: Medical students from resource-rich countries who rotate in resource-limited settings have little pre-departure experience performing procedures, and lack familiarity with local equipment. The risk of blood and body fluid exposures during such rotations is significant. AIM: 1) Determine whether a simulation-based intervention reduced exposures among US medical students on a rotation in Botswana; 2) determine whether exposures were underreported; 3) describe exposures and provision of human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP). SETTING: University of Pennsylvania medical students who traveled to Botswana for a clinical rotation from July 2007 to February 2010 were eligible to participate. PROGRAM DESCRIPTION: Twenty-two students participated in the simulation-based intervention. PROGRAM EVALUATION: To evaluate the intervention, we used a pre/post quasi-experimental design and administered a retrospective survey. The response rate was 81.7% (67/82). Needlesticks were eliminated [8/48 (16.7%) to 0/19 (0.0%), p = 0.07]. Splashes were unchanged (6/48 [12.5%) to 3/19 (15.8%), p=>0.99]. Three students did not report their exposure. Fifteen exposures were reported to an attending, who counseled the student regarding HIV PEP. Three students did not take PEP because the exposure was low-risk. DISCUSSION: Our intervention was associated with a decrease in needlestick exposures. Medical schools should consider training to reduce exposures abroad.

Comparative genomic analyses identify the Vibrio harveyi genome sequenced strains BAA-1116 and HY01 as Vibrio campbellii.

Three notable members of the Harveyi clade, Vibrio harveyi, Vibrio alginolyticus and Vibrio parahaemolyticus, are best known as marine pathogens of commercial and medical import. In spite of this fact, the discrimination of Harveyi clade members remains difficult due to genetic and phenotypic similarities, and this has led to misidentifications and inaccurate estimations of a species' involvement in certain environments. To begin to understand the underlying genetics that complicate species level discrimination, we compared the genomes of Harveyi clade members isolated from different environments (seawater, shrimp, corals, oysters, finfish, humans) using microarray-based comparative genomic hybridization (CGH) and multilocus sequence analyses (MLSA). Surprisingly, we found that the only two V. harveyi strains that have had their genomes sequenced (strains BAA-1116 and HY01) have themselves been misidentified. Instead of belonging to the species harveyi, they are actually members of the species campbellii. In total, 28% of the strains tested were found to be misidentified and 42% of these appear to comprise a novel species. Taken together, our findings correct a number of species misidentifications while validating the ability of both CGH and MLSA to distinguish closely related members of the Harveyi clade.

The impact of the internal medicine sub-internship on medical student career choice.

BACKGROUND: Medical student interest in internal medicine is decreasing. Whether the internal medicine sub-internship affects intent to pursue internal medicine is unknown. OBJECTIVE: Determine the immediate and longer-term effect of the medicine sub-internship on students' decision to pursue internal medicine residency. DESIGN: Mixed method, single institution, prospective cohort study. PARTICIPANTS: Ninety-two students completing an internal medicine sub-internship in 2006. MEASUREMENTS: Survey administered prior to and immediately after the sub-internship and prior to the match. Questions included likelihood of applying in internal medicine and perceived impact of the sub-internship on career choice. MAIN RESULTS: Seventy-seven percent of students (N = 63) completed the first two surveys; 63% (N = 58) completed the second and third. Immediately post sub-internship, 21% (N = 13) were less likely to apply in internal medicine and 11% (N = 7) were more likely to apply (net change in plans was not significant, p = 0.38). There was a significant relationship between the perceived impact of the sub-internship and likelihood of applying in medicine (ANOVA comparison across means, p < 0.001). Compared to the second survey, on the third survey more students (41%, N = 24) believed the sub-internship positively impacted their decision to apply in medicine, though overall shifting was not significant (p = 0.39). Key themes describing sub-internship impact included the intense workload, value of experiencing internship, rewards of assuming the physician role, and education received (30%, 25%, 20% and 16% of comments, respectively). CONCLUSIONS: Overall, there was not a significant effect of the sub-internship on students' decision to apply in internal medicine. Additional research about the relative impact of the sub-internship in relationship to other career choice predictors is needed to better address factors that may encourage or dissuade students from pursuing internal medicine.

Professionalism in clerkships: an analysis of MSPE commentary.

BACKGROUND: Professionalism in medical school predicts future behaviors. The authors assessed prevalence of references to professionalism behaviors in the clerkship commentary portion of Medical School Performance Evaluations (MSPEs). METHOD: Content analyses of 293 MSPEs submitted for 2005 graduates. RESULTS: Overall, 70% of MSPEs specifically mentioned professionalism; 96% included information about at least 1 of 16 professional behaviors. Internal Medicine referenced significantly more behaviors than other clerkships. Commentary about behaviors such as interactions (94%) and motivation (91%) was common; behaviors such as truthfulness (8%) and confidentiality (6%) were rarely mentioned. Fewer than 1% of comments could be considered negative. CONCLUSIONS: Most professionalism comments in MSPEs are generic and somewhat bland, tending to be about students' collegial interactions and hard work. More detail and breadth may be facilitated by wider use of behavior-centered evaluation in clerkships.

Medical Student Performance Evaluations in 2005: an improvement over the former dean's letter?

PURPOSE: To collect information regarding preparation, content, and format of Medical Student Performance Evaluations (MSPEs) and evaluate a sample of 2005 MSPEs to assess compliance with the 2002 Association of American Medical Colleges-issued MSPE guidelines. METHOD: Cross-sectional survey with all 126 U.S. allopathic medical schools. Associate deans of students affairs were sent an eight-item questionnaire in June 2006 and asked to submit a sample of redacted MSPEs for 2005 graduates, choosing one from each tertile of the class. Survey data are summarized. MSPEs were abstracted, and results are presented descriptively. RESULTS: The survey response rate was 84%. Most associate deans (71%) reported having primary responsibility for composing MSPEs; 78% adhered to the format and content guidelines three fourths of the time. The abstraction of 293 MSPEs (78%) showed that more than 80% adhered to format recommendations. However, only 70% to 80% stated grades clearly, avoided the word recommendation, and stated whether the student had completed remediation. Fewer than 70% indicated whether the student had had any adverse actions or provided adequate comparative data. Strikingly, only 17% provide comparative data in the summary paragraph. Overall, 75% of the MSPEs were judged to be "adequate." CONCLUSIONS: MSPEs are somewhat variable in terms of which specific items are included. There has been steady quality improvement since prior surveys, primarily in formatting and labeling. However, a sizable minority of writers are still using the MSPE as a recommendation, and too few are providing helpful comparative data.

Mutations in the lux operon of natural dark mutants in the genus Vibrio.

Bacterial bioluminescence can display a wide range of intensities among strains, from very bright to undetectable, and it has been shown previously that there are nonluminous vibrios that possess lux genes. In this paper, we report the isolation and characterization of completely dark natural mutants in the genus Vibrio. Screening of over 600 Vibrio isolates with a luxA gene probe revealed that approximately 5% carried the luxA gene. Bioluminescence assays of the luxA-positive isolates, followed by repetitive extragenic palindromic-PCR fingerprinting, showed three unique genotypes that are completely dark. The dark mutants show a variety of lesions, including an insertion sequence, point mutations, and deletions. Strain BCB451 has an IS10 insertion sequence in luxA, a mutated luxE stop codon, and a truncated luxH. Strain BCB494 has a 396-bp deletion in luxC, and strain BCB440 has a frameshift in luxC. This paper represents the first molecular characterization of natural dark mutants and the first demonstration of incomplete lux operons in natural isolates.

Experimental and theoretical studies of charge transfer and deuterium ion transfer between D2O+ and C2H4.

The charge transfer and deuterium ion transfer reactions between D(2)O(+) and C(2)H(4) have been studied using the crossed beam technique at relative collision energies below one electron volt and by density functional theory (DFT) calculations. Both direct and rearrangement charge transfer processes are observed, forming C(2)H(4) (+) and C(2)H(3)D(+), respectively. Independent of collision energy, deuterium ion transfer accounts for approximately 20% of the reactive collisions. Between 22 and 36 % of charge transfer collisions occur with rearrangement. In both charge transfer processes, comparison of the internal energy distributions of products with the photoelectron spectrum of C(2)H(4) shows that Franck-Condon factors determine energy disposal in these channels. DFT calculations provide evidence for transient intermediates that undergo H/D migration with rearrangement, but with minimal modification of the product energy distributions determined by long range electron transfer. The cross section for charge transfer with rearrangement is approximately 10(3) larger than predicted from the Rice-Ramsperger-Kassel-Marcus isomerization rate in transient complexes, suggesting a nonstatistical mechanism for H/D exchange. DFT calculations suggest that reactive trajectories for deuterium ion transfer follow a pathway in which a deuterium atom from D(2)O(+) approaches the pi-cloud of ethylene along the perpendicular bisector of the C-C bond. The product kinetic energy distributions exhibit structure consistent with vibrational motion of the D-atom in the bridged C(2)H(4)D(+) product perpendicular to the C-C bond. The reaction quantitatively transforms the reaction exothermicity into internal excitation of the products, consistent with mixed energy release in which the deuterium ion is transferred in a configuration in which both the breaking and the forming bonds are extended.