Percutaneous retrieval of fractured intravascular catheters in premature infants.

BACKGROUND: Premature infants often require long-term indwelling intravascular catheters. Occasionally, catheters fracture and migrate into cardiovascular structures, risking perforation, infection, thrombosis, and interference with cardiac and valve function. This case series describes our experience with percutaneous retrieval of broken intravascular catheters. METHODS: A gooseneck micro-snare was used to retrieve fractured catheters in four premature infants, weighing between 840 and 1930 grams. RESULTS: All procedures were successful without complications. CONCLUSIONS: Gooseneck-snare retrieval of broken indwelling intravascular catheters can be performed safely and successfully in premature infants even those that weigh less than 1000 grams.

An actuatable soft reservoir modulates host foreign body response.

The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices-including breast implants, biosensors, and drug delivery devices-are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials.

Eating disorder professionals' perceptions of oral health knowledge.

OBJECTIVE: The aim of this study was to assess the oral health knowledge among professionals who specialize in treating eating disorders, and identify to what extent their education, and training addresses oral health care delivery, and recommendations for individuals with eating disorders. METHOD: Participants for this study were licensed behavioural and medical providers specializing in eating disorder treatment (n = 107), and recruited through professional eating disorder organizations. Participants completed an anonymous, online questionnaire (33 items) assessing level of oral health-related education, knowledge and treatment recommendations within the participant's respective eating disorder discipline. RESULTS: The majority of respondents (85%) were formally trained in eating disorders, and of those trained, 64.4% were not satisfied with the level of oral health education during formal education, and 19.5% report no oral health education. Respondents consider their knowledge of risk of oral disease for their clients/patients as average or above (84%), and ranked tooth erosion as the greatest reason for oral care (63%) while dry mouth led in the rankings for least significant reason for oral care (33%). Referral for oral care was found to be more common after reports of complication (55%). DISCUSSION: According to these findings, eating disorder professionals regard oral health care for their clients as significant, and may be unaware of associated oral risk factors, current oral care standards and long-term oral effects of disordered eating apart from enamel erosion.

Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells.

Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes.

Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.

To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5-6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long-term PEG-IFN treatment.

Overlapping covered stents to exclude a postcoarctation stenting aortic aneurysm.

An 18-year-old boy who underwent coil occlusion of a patent ductus arteriosus and stenting for aortic coarctation at 13 years of age had evidence of re-stenosis. Cardiac catheterization and angiography showed a 25-mmHg gradient across the stent and a large aneurysm originating at midstent level. The aneurysm measured 2 cm in width and 4.3 cm in length. At a subsequent catheterization procedure, two 4.5-cm-long overlapping Cheatham platinum covered stents were implanted, completely excluding the aneurysm. Computed tomographic (CT) angiography 2 years later showed no evidence of endoleak or re-stenosis.

Enlarged left vitelline vein remnant as a cause of cyanosis after the Fontan procedure: resolution with an Amplatzer vascular plug.

A 6-year-old girl with heterotaxy and a functional single ventricle had persistent cyanosis 4 years after a fenestrated Fontan procedure. Cardiac catheterization revealed a large venous fistula from a left-sided hepatic vein to the coronary sinus, resulting in desaturation. The anomalous vein was occluded with an Amplatzer vascular plug.

Upper extremity peripheral venous pressure measurements accurately reflect pulmonary artery pressures in patients with cavopulmonary or Fontan connections.

After the bidirectional cavopulmonary or Fontan operation, the physiologic consequence is passive flow of the systemic venous return to the pulmonary arteries. Knowledge of pulmonary artery pressure (PA) is valuable in the management of these patients, and obtaining this information without the need for a central line or cardiac catheterization would be advantageous. The aim of this study was to evaluate the correlation between upper extremity peripheral venous (PV) pressures and PA or superior vena cava (SVC) pressures in patients who have undergone cavopulmonary or Fontan connections. During cardiac catheterization, 19 patients with complex cyanotic heart disease who had undergone a cavopulmonary shunt or Fontan procedure were studied. Simultaneous pressure measurements were obtained from the peripheral intravenous line placed prior to the procedure and the SVC or PA. The mean pressures were compared. The mean PV pressure was 17.5 +/- 5.6 mmHg. The mean SVC or PA pressure was 16.1 +/- 5.4 mmHg. The mean difference was 1.5 +/- 1.5 mmHg ( p < 0.001). The correlation coefficient PV to SVC or PA pressure was 0.97 ( p < 0.001). PV pressure measurements taken from an upper extremity accurately reflect PA pressures in patients who have undergone a cavopulmonary shunt or Fontan procedure.

HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais.

Little is known of the role of classical HLA-A and -B class I alleles in determining resistance, susceptibility, or the severity of acute viral infections. Appropriate paradigms for immunogenetic studies of acute viral infections are dengue fever (DF) and dengue hemorrhagic fever (DHF). Both primary and secondary infections with dengue virus (DEN) serotypes 1, 2, 3 or 4, can result in either clinically less severe DF or the more severe DHF. In secondary exposures, a memory response is induced in immunologically primed individuals, which can both clear the infecting dengue virus and contribute to its pathology. In a case-control study of 263 ethnic Thai patients infected with either DEN-1, -2, -3 or -4, we detected HLA class I associations with secondary infections, but not in immunologically naive patients with primary infections. HLA-A*0203 was associated with the less severe DF, regardless of the secondary infecting virus serotype. By contrast, HLA-A*0207 was associated with susceptibility to the more severe DHF in patients with secondary DEN-1 and DEN-2 infections only. Conversely, HLA-B*51 was associated with the development of DHF in patients with secondary infections, and HLA-B*52 was associated with DF in patients with secondary DEN-1 and DEN-2 infections. Moreover, HLA-B44, B62, B76 and B77 also appeared to be protective against developing clinical disease after secondary dengue virus infection. These results confirm that classical HLA class I alleles are associated with the clinical outcome of exposure to dengue virus, in previously exposed and immunologically primed individuals.

The Challenge study: theory-based interventions for smoking and weight loss.

Both smokers and overweight persons report frequent efforts to change their behavior. Long-term success, however, is achieved by few. Interventions are needed to improve long-term success in smoking cessation and weight loss. Our research program is designed to address this need and to test a novel conceptualization of health behavior change that is based on the premise that the initiation and the maintenance of behavior change involve different decision processes. Positive expectations about the consequences of behavior change are thought to guide decisions to initiate behavior change, whereas satisfaction with the outcomes afforded by one's behavior guides decisions about maintenance. In the first phase of our research program, we are evaluating the effect people's expectations about the benefits of behavior change have on immediate and long-term behavioral outcomes. Specifically, participants are assigned to either an 'optimistic' treatment condition that emphasizes positive expectations for outcomes or a 'balanced' treatment condition that gives equal weight to the benefits and costs associated with behavior change. The impact of manipulating people's expectations about behavior change will be examined in the areas of smoking cessation and weight loss. Results of these studies will advance research on health behavior change by informing practical and theoretical understanding of the factors that control decisions to initiate a new pattern of behavior and to maintain it.

Ambiguity and mistakes in the pediatric cardiology vernacular.

The pediatric cardiology vernacular is replete with ambiguous and erroneous terminology. This article discusses several examples in a plea to bring the accuracy and precision of the scientific method to the clinical pediatric cardiology vernacular.

Efficient metaphase II transgenesis with different transgene archetypes.

Mammalian genome characterization and biotechnology each require the mobilization of large DNA segments to produce transgenic animals. We recently showed that mouse metaphase II (mII) oocytes could efficiently promote transgenesis (mII transgenesis) when coinjected with sperm and small (<5 kilobases) ubiquitously expressed transgenes (tgs). We have extended this work and now report that mII transgenesis can readily be applied to a range of larger tgs (11.9-170 kilobases), including bacterial and mammalian artificial chromosome (BAC and MAC) constructs. The efficiency of large-construct mII transgenesis was at least as high as that with small constructs; 11-47% of offspring carried the large tgs. More than 95% of these transgenic founders transmitted the tg to offspring. These data demonstrate the ability of mII transgenesis to deliver large tgs efficiently.

Atrial septostomy for pulmonary hypertension.

Atrial septostomy represents an additional, promising strategy in the treatment of severe PPH. Experience with this procedure still is limited; however, based on analyses of the worldwide experience, several general conclusions and recommendations can be made. 1. Atrial septostomy can be performed successfully in selected patients with advanced pulmonary vascular disease. 2. Patients with primary pulmonary hypertension who have undergone successful AS have shown: a significant clinical improvement beneficial and long-lasting hemodynamic effects at rest a trend toward improved survival 3. The procedure-related mortality of the collective experience is high (16%). Several recommendations can be made to minimize the risk: [figure: see text] Atrial septostomy should be attempted only in institutions with an established track record in the treatment of advanced pulmonary hypertension, where septostomy is performed with low morbidity. Atrial septostomy should not be performed in patients in whom death is impending or who have severe right ventricular failure and are on maximal cardiorespiratory support. An mRAP greater than 20 mm Hg, PVR index greater than 55 u/m2, and a predicted 1-year survival less than 40% are significant predictors of procedure-related death. Before cardiac catheterization, patients should have an acceptable baseline systemic oxygen saturation (> 90% in room air) and optimized cardiac function (adequate right heart filling pressure, additional inotropic support if necessary). During cardiac catheterization, the following are mandatory: Supplemental oxygen Mild sedation to prevent anxiety Careful monitoring of variables (left atrial pressure, SaO2, and mRAP) Step by step procedure After AS, it is important to optimize oxygen delivery. Transfusion of packed red blood cells or erythropoietin (before and following the procedure, if needed) may be necessary to increase oxygen content. 4. Because the disease process in PPH is unaffected by the procedure (late deaths), the long-term effects of an AS must be considered to be palliative. 5. Despite its risk, AS may represent a viable alternative for selected patients with severe PPH. Indications for the procedure may include: Recurrent syncope or right ventricular failure, despite maximal medical therapy, including oral calcium-channel blockers or continuous intravenous prostacyclin (Fig. 11) As a bridge to transplantation When no other option exists.

c-Jun decreases voltage-gated K(+) channel activity in pulmonary artery smooth muscle cells.

BACKGROUND: Activity of voltage-gated K(+) (K(v)) channels controls membrane potential (E(m)) that regulates cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) by regulating voltage-dependent Ca(2+) channel function. A rise in [Ca(2+)](cyt) in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a transcription factor that stimulates cell proliferation, affects K(v) channel activity in PASMCs was investigated. METHODS AND RESULTS: Infection of primary cultured PASMCs with an adenoviral vector expressing c-jun increased the protein level of c-Jun and reduced K(v) currents (I(K(V))) compared with control cells (infected with an empty adenovirus). Using single-cell reverse transcription-polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the current density of I(K(V)) were both attenuated in c-jun-infected PASMCs compared with control cells and cells infected with antisense c-jun. Overexpression of c-Jun also upregulated protein expression of Kvbeta(2) and accelerated I(K(V)) inactivation. Furthermore, E(m) was more depolarized and [(3)H]thymidine incorporation was greater in PASMCs infected with c-jun than in control cells and cells infected with antisense c-jun. CONCLUSIONS: These results suggest that c-Jun-mediated PASMC proliferation is associated with a decrease in I(K(V)). The resultant membrane depolarization increases [Ca(2+)](cyt) and enhances PASMC growth.

Reptilian echocardiography: insights into ontogeny and phylogeny?

We describe the echocardiographic findings in a large reptile-the carpet python. If ontogeny recapitulates phylogeny, the study of reptilian hearts may provide insights into human cardiac development. In addition, the reptilian heart has unique structural and physiological adaptations that may broaden our perspective on evolutionary cardiac adaptation.

Induction of T lymphocyte responses to dengue virus by a candidate tetravalent live attenuated dengue virus vaccine.

Development of a safe and immunogenic tetravalent dengue virus (DV) vaccine has been designated as a priority by the World Health Organization. We characterized the T cell response to DV induced by a candidate live attenuated tetravalent DV vaccine as part of a phase I study. Proliferation and cytotoxic T lymphocyte (CTL) responses to multiple DV serotypes were detected in six of six and four of four subjects studied, respectively. Proliferation responses were higher to DV serotypes 1 and 3 than to serotypes 2 and 4. CTL responses were higher to DV serotypes 2 and 3 than to serotype 1, and included serotype cross-reactive responses. Production of interferon-gamma, but not IL-4, was observed in response to DV stimulation. This candidate vaccine is immunogenic for both CD4+ and CD8+ T lymphocytes. However, T cell responses to the four DV serotypes were not equivalent, suggesting that the vaccine could be further optimized.

MIP-1 alpha and MIP-1 beta induction by dengue virus.

Dengue virus (DV) infection can result in either a mild febrile illness known as dengue fever (DF) or a life-threatening disease called dengue hemorrhagic fever (DHF). DHF is more prevalent in patients undergoing secondary DV infection. This observation has led to the hypothesis that DHF may be the result of immune reactions to the secondary DV infection; an event termed immunopathology. Two cellular factors, MIP-1 alpha and MIP-1 beta, have been found to be induced by infection with DV. MIP-1 induction by DV infection was observed in a myelomonocytic cell line, as well as in peripheral blood mononuclear cells isolated from a dengue naive donor. MIP-1 induction was not due to factors secreted by infected cells. In fact, replication-competent virus was required to induce MIP-1. Evidence is also provided that MIP-1 genes are expressed in patients with dengue disease. It is hypothesized that these chemokines may have roles in the immunopathology of dengue infections and may contribute to fever and bone marrow suppression observed in patients with DV infections.

The effects of message framing and ethnic targeting on mammography use among low-income women.

The authors examined the effects that differently framed and targeted health messages have on persuading low-income women to obtain screening mammograms. The authors recruited 752 women over 40 years of age from community health clinics and public housing developments and assigned the women randomly to view videos that were either gain or loss framed and either targeted specifically to their ethnic groups or multicultural. Loss-framed, multicultural messages were most persuasive. The advantage of loss-framed, multicultural messages was especially apparent for Anglo women and Latinas but not for African American women. These effects were stronger after 6 months than after 12 months.

Assessment of English proficiency in international medical graduates by physician examiners and standardized patients.

CONTEXT: Since 1986, the Ontario Ministry of Health has provided a medical licensure preparation programme for international medical graduates. Because of the diversity in candidates' oral English proficiency, this competency has been viewed as a particularly important selection criterion. OBJECTIVES: To assess and compare the quality of ratings of oral English proficiency of international medical graduates provided by physician examiners and by standardized patients (SPs). PARTICIPANTS AND MATERIALS: The study samples consisted of 73 candidates for the Ontario International Medical Graduate (IMG) Program, and physician examiners and SPs in five 10-minute encounter objective structured clinical examination (OSCE) stations. Materials used were a seven-item speaking performance rating instrument prepared for the Ontario IMG Program. METHODS: Rating sheets were scanned and the results analysed using SPSS 9.0 for Windows. RESULTS: Correlations between the physician and SP ratings on the seven items ranged from 0.52 to 0.70. The SPs provided more lenient ratings. Mean alpha reliability for the physicians' ratings on the seven items was 0.59, and for the SPs' 0.64. There was poor agreement between the two sets of raters in identifying problematic candidates. CONCLUSIONS: Notwithstanding the sizable correlations between the ratings provided by the two rater groups, the results demonstrated that there was little agreement between the two groups in identifying the potentially problematic candidates. The physicians were less prone than the SPs to rate candidates as problematic. SPs may be better placed than the physician examiners to directly assess IMG candidates' oral English proficiency.