Triiodothyronine supplementation in a sheep model of intensive care.

Triiodothyronine (T3) concentrations in plasma decrease during acute illness and it is unclear if this contributes to disease. Clinical and laboratory studies of T3 supplementation in disease have revealed little or no effect. It is uncertain if short term supplementation of T3 has any discernible effect in a healthy animals. Observational study of intravenous T3 (1 µg/kg/h) for 24 h in a healthy sheep model receiving protocol-guided intensive care supports (T3 group, n=5). A total of 45 endpoints were measured including hemodynamic, respiratory, renal, hematological, metabolic and endocrine parameters. Data were compared with previously published studies of sheep subject to the same support protocol without administered T3 (No T3 group, n=5). Plasma free T3 concentrations were elevated 8-fold by the infusion (pmol/l at 24 h; T3 group 34.9±9.9 vs. No T3 group 4.4±0.3, P<0.01, reference range 1.6 to 6.8). There was no significant physiological response to administration of T3 over the study duration. Supplementation of intravenous T3 for 24 h has no physiological effect on relevant physiological endpoints in healthy sheep. Further research is required to understand if the lack of effect of short-term T3 may be related to kinetics of T3 cellular uptake, metabolism and action, or acute counterbalancing hormone resistance. This information may be helpful in design of clinical T3 supplementation trials.

Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model.

Irinotecan eluting embolization beads (DEBIRI) are currently being evaluated in the clinic for the treatment of colorectal cancer metastases to the liver. The aim of this study was to determine the safety and pharmacokinetics associated with two cycles of hepatic embolization using DEBIRI followed by intravenous administration of irinotecan. Pigs were embolized with DEBIRI (100-300 µm, 100 mg dose, n = 6) and blood samples taken over 24 h to determine plasma levels of irinotecan and SN-38 metabolite and for haematology and biochemistry. At 24 h an IV infusion of 250 mg/m(2) of irinotecan was administered and the plasma levels taken again. This cycle was repeated 3 weeks later. A single animal was subjected to a more aggressive regimen of embolization with 200 mg bead dose and IV of 350 mg/m(2) for two cycles. Three animals were sacrificed at 6 weeks and the remaining four (n = 3 standard dose, n = 1 high dose) animals at 12 weeks and detailed histopathology performed. All animals tolerated the treatments well, with only minor changes in haematological and biochemical parameters. There was no overlap in drug plasma levels observed from the bead and IV treatments when given 24 h apart and no difference between the pharmacokinetic profiles of the two cycles separated by 3 weeks. Irinotecan plasma AUC values were similar in both the embolization and IV arms of the study. C(max) values obtained during the IV arms of the study are approximately double that of the embolization arms whilst T(max) times are shorter in the IV arms, supporting extended release of drug from the beads. Bioavailability for bead-based delivery was double that for IV administration, which was attributed to reduced clearance of the drug when delivered by this route. No additive toxicity was observed as a consequence of the combined treatments. The combination of irinotecan delivery via drug eluting bead and IV was well-tolerated with no significant clinical effects. Pharmacokinetic analyses suggest the bioavailability from bead-based delivery of drug is double that of IV infusion, attributable to reduced drug clearance for the former.

Characterizing the knowledge of educators across the tiers of instructional support.

Translating the research base on effective reading instruction to the classroom has been a challenge. The delivery of these instructional methods requires practical skills coupled with an understanding of the aspects of language being taught. The purpose of this study was to explore the level of literacy knowledge of the English language held by educators who provide instruction to students in the primary grades. Data from 1369 classroom teachers, 74 reading interventionists, and 131 special educators comprising the analytic sample were collected as part of a training initiative in a US state. Participating educators completed a 50-item test of phonological sensitivity, phonemic awareness, decoding, encoding, and morphology. Multiple regression analyses confirmed differences in the levels of knowledge observed between the groups of educators. Reading interventionists demonstrated greater knowledge than classroom teachers and special educators in the total proportion of correct responses and across each domain. Classroom teachers demonstrated greater knowledge than special educators in phonological sensitivity and decoding but did not differ from each other in phonemic awareness, encoding, or morphology knowledge. Special educators provide intervention to students with the most severe forms of reading disabilities, yet they had the lowest level of knowledge. In contrast, reading interventionists, who provide intervention within general education, had the highest levels of knowledge. These findings suggest a need to elevate the knowledge of special educators and consider reading interventionists' role in supporting students identified with a specific learning disability in reading.

"Scrub the hub": cleaning duration and reduction in bacterial load on central venous catheters.

This article reports the results of a study on the effect of alcohol disinfection duration on bacterial load on catheter hubs. Three different levels of disinfection (3, 10, and 15 seconds) were analyzed as well as a positive and negative control. All hubs with the exception of the negative controls were contaminated with a 10 bacterial solution and allowed to dry for 24 hours. Through each hub, 1 mL of sterile saline was flushed; a 10-µL calibrated loop was used to plate the flush onto blood agar. Colony counts were performed on the plates after a 24-hour incubation period. Results revealed that the 3 different levels of disinfection duration were not found to differ significantly in reduction in bacterial load. The duration of disinfection did not significantly change the bacterial load on the hub. However, any disinfection duration significantly decreased the bacterial load as compared to the positive control. A larger study would likely detect a significant result among the disinfections.

Community-associated CMRSA-10 (USA-300) is the predominant strain among methicillin-resistant Staphylococcus aureus strains causing skin and soft tissue infections in patients presenting to the emergency department of a Canadian tertiary care hospital.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen first described among individuals with no contact with health care facilities. The purpose of this study was to determine the proportion of CA-MRSA, defined by pulsed field gel electrophoresis (PFGE), in MRSA skin and soft tissue infections presenting to the Emergency Department (ED). We also aimed to describe the laboratory and clinical characteristics of CA-MRSA infections. From June 1, 2001 to May 30, 2005, MRSA isolates from skin and soft tissue infections presenting to the ED were reviewed. They were characterized by antibiotic susceptibilities and PFGE, and the presence of staphylococcal cassette chromosome (SCC) mec type IVa and Panton-Valentine leukocidin (PVL) genes was assessed on representative isolates. The medical records were reviewed to define risk factors. There were 95 isolates available for analysis, of which 58 (61%) were CMRSA-10 (USA-300), the predominant clone from 2003 onward. All representative isolates (24%) tested in this group had PVL genes and SCCmec type IVa. Their antibiogram showed 100% susceptibility to trimethoprim-sulfamethoxazole, rifampin, and fusidic acid, and 79% to clindamycin. Clinical comparison of CMRSA-10 vs. hospital PFGE type strains showed 22% vs. 60%, respectively, for recent antibiotic use (p < 0.0001), 26% vs. 6%, respectively, for intravenous drug use (p < 0.05), and 57% vs. 6%, respectively, for soft tissue abscess (p < 0.001). CMRSA-10 is a major pathogen in skin and soft tissue abscesses in our ED. It has a characteristic susceptibility, and was associated with intravenous drug use, but not with recent antibiotic usage.

Neuralgic Amyotrophy Attributed Incorrectly to Block-Related Injury: Understanding Errors in Clinical Reasoning.

OBJECTIVE: We report a case of misdiagnosed neuralgic amyotrophy (brachial plexus neuritis, Parsonage-Turner syndrome). Our primary objective is to review the scientific basis for errors in clinical reasoning. CASE REPORT: We herein report a patient in whom signs and symptoms compatible with neuralgic amyotrophy presented after shoulder surgery. The patient's brachial plexopathy was attributed incorrectly as a complication of interscalene brachial plexus block. The true diagnosis was made only after the patient developed neuralgic amyotrophy in the contralateral upper extremity after a subsequent shoulder surgery on that side, this time without a brachial plexus block. CONCLUSIONS: Cognitive bias may lead to errors in clinical reasoning and consequent misdiagnosis. Temporal proximity may falsely implicate regional anesthesia as the causative agent.

Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells.

Growth factor independence-1 (GFI1) and GFI1B are closely related, yet differentially expressed transcriptional repressors with nearly identical DNA binding domains. GFI1 is upregulated in the earliest thymocyte precursors, while GFI1B expression is restricted to T lymphopoiesis stages coincident with activation. Transgenic expression of GFI1 potentiates T-cell activation, while forced GFI1B expression decreases activation. Both mice and humans with mutant Gfi1 display lymphoid abnormalities. Here we describe autoregulation of Gfi1 in primary mouse thymocytes and a human T-cell line. GFI1 binding to cis-element sequences conserved between rat, mouse and human Gfi1 mediates direct and potent transcriptional repression. In addition, dramatic regulation of Gfi1 can also be mediated by GFI1B. These data provide the first example of a gene directly targeted by GFI1 and GFI1B. Moreover, they support a role for auto- and trans-regulation of Gfi1 by GFI1 and GFI1B in maintaining the normal expression patterns of Gfi1, and suggest that GFI1B may indirectly affect T-cell activation through repression of Gfi1.

Uterine prolapse with endometrial eversion in association with an unusual diffuse, polypoid, fibrosing perimetritis and parametritis in a cat.

CASE SUMMARY: This case describes a young non-pregnant cat that presented with uterine prolapse in association with an unusual diffuse, polypoid, fibrosing perimetritis and parametritis. Following ovariohysterectomy the cat recovered fully. No intra-abdominal complications were seen on ultrasound examination 3 months postsurgery. At the time of writing, the cat remains healthy. RELEVANCE AND NOVEL INFORMATION: Uterine prolapse in the cat is relatively rare and usually associated with the periparturient period. Inflammatory polypoid perimetritis and parametritis have not previously been documented in cats, and in dogs have only been reported in association with the administration of oestrogenic compounds. The polypoid inflammation affecting the uterus and parametrium may have contributed to increased laxity of the uterine ligaments and predisposed to the development of uterine prolapse.

Using mixed reality, force feedback and tactile augmentation to improve the realism of medical simulation.

This paper describes an application of a display approach which uses chromakey techniques to composite real and computer-generated images allowing a user to see his hands and medical instruments collocated with the display of virtual objects during a medical training simulation. Haptic feedback is provided through the use of a PHANTOM force feedback device in addition to tactile augmentation, which allows the user to touch virtual objects by introducing corresponding real objects in the workspace. A simplified catheter introducer insertion simulation was developed to demonstrate the capabilities of this approach.

Inadequacy of IgM antibody tests for diagnosis of Rocky Mountain Spotted Fever.

Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States.

In vivo and in vitro potency studies of 6beta-naltrexol, the major human metabolite of naltrexone.

Naltrexone, a mu opioid receptor antagonist, is used in the treatment of opioid and alcohol dependence. Naltrexone's longer duration of action compared to naloxone has been considered to be due partly to its major human metabolite, 6beta-naltrexol. To date, no studies have examined the in vitro or in vivo potency of 6beta-naltrexol compared to naltrexone and naloxone. In the electrically-stimulated guinea pig ileum, 6beta-naltrexol was more potent (K(i) = 94 +/- 25 pM), than naloxone (420 +/- 150 pM), and naltrexone (265 +/- 101 pM). In vivo comparative potencies were assessed using the mouse hotplate test and morphine (agonist), with doses of the antagonists from 0.001 to 30 mg/kg. The order of potency was naltrexone (ID(50) 7 microg/kg), naloxone (ID(50) 16 microg/kg) and 6beta-naltrexol (ID(50) 1300 microg/kg). Antagonist ID(50) doses were then administered at 45, 90, 120, 180 and 1080 minutes prior to morphine administration. The duration of antagonist activity to decrease by 50% was 80, 125 and 340 minutes for naltrexone, naloxone and 6beta-naltrexol, respectively. 6beta-naltrexol is highly potent in the guinea pig ileum, but much less so in vivo after an acute dose. However, the potency of 6beta-naltrexol in vivo is time-dependent, and it has a longer duration of action than naloxone and naltrexone, consistent with a pharmacokinetic longer terminal half-life. Therefore, 6beta-naltrexol is likely to contribute to the efficacy of naltrexone in humans.

An outbreak of community-acquired foodborne illness caused by methicillin-resistant Staphylococcus aureus.

Infections with methicillin-resistant Staphylococcus aureus (MRSA) are increasingly community acquired. We investigated an outbreak in which a food handler, food specimen, and three ill patrons were culture positive for the same toxin-producing strain of MRSA. This is the first report of an outbreak of gastrointestinal illness caused by community-acquired MRSA.