Biomedical subjects

A Rothman

Publications and source records attributed to A Rothman.

At least 19 recordsLinked to original sources

PubMed2003

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.

Adolescent↗

PubMed2001

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.

Adenoviridae↗

PubMed2001

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.

Cardiac Surgical Procedures↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Adaptation, Physiological↗

PubMed2001

Staying up-to-date through distance education: the radiation therapy perspective.

BACKGROUND: Distance education (DE) courses are offered to medical radiation technologists (therapy) [MRT(T)] in Canada for professional development (PD). METHODS: A survey of 300 therapists was conducted to identify potential participants and factors that can influence DE participation and learning. RESULTS: The motivation to take PD is intrinsic, for personal growth and fulfillment, rather than to satisfy employment or provincial requirements. There is interest in DE because of its accessibility. Work constraints appear to be more restrictive than domestic ones and little support for PD is perceived from the cancer centers. CONCLUSIONS: These findings raise implications for professional development in cancer centers that are broader than the original objective of optimizing course design.

Adult↗

PubMed2001

Inhibition of K(+) channel activity in human pulmonary artery smooth muscle cells by serum from patients with pulmonary hypertension secondary to congenital heart disease.

Activity of K(+) channels regulates cytosolic free Ca(2+) concentration by controlling membrane potential. A rise in cytosolic free Ca(2+) concentration in pulmonary artery smooth muscle cells (PASMC) triggers pulmonary vasoconstriction and stimulates PASMC proliferation. Whether serum from children with pulmonary hypertension (PH) secondary to congenital cardiopulmonary diseases contains a factor(s) that inhibits K(+) channel function in PASMC was investigated using patch clamp techniques. PASMC isolated from normal subjects were cultured in media containing 5% serum from normotensive (NPH) or PH patients. Cell growth rate and the currents through voltage-gated K(+) channels were determined and compared between the cells treated with serum from NPH and PH patients. In the absence of growth factors, incubation of PASMC in media containing NPH serum for 48 h increased cell numbers by 2.5-fold, whereas incubation of the cells in media containing PH serum increased cell numbers by 4.5-fold (p < 0.001). Amplitude of whole-cell voltage-gated K(+) currents in NPH serum-treated cells (1119 +/- 222 pA at +80 mV, n = 43) was 3.5-fold greater than in PH serum-treated cells (323 +/- 34 pA, n = 43, p < 0.001). Consistently, membrane potential was much more depolarized in PASMC treated with PH serum (-28 +/- 2 mV, n = 29) than cells treated with NPH-serum (-47 +/- 2 mV, n = 28; p < 0.001). These results suggest that a circulating mitogenic agonist, which induces membrane depolarization by inhibiting voltage-gated K(+) channel activity in PASMC, may be produced or up-regulated in pediatric patients with secondary PH.

Blood↗

PubMed2000

Evaluation of calibration methods for size estimation in the pediatric cardiac catheterization laboratory.

Limited data are available on the accuracy of various calibration methods used to estimate the size of cardiovascular structures during interventional pediatric cardiac catheterizations. The aim of this study was to evaluate, in an experimental model, several of these commonly used calibration methods. Thoracic box models were constructed in 4 sizes to simulate average chest sizes of infants, children, adolescents, and adults. Four anatomic positions were studied: aortic valve in posteroanterior projection, pulmonary valve in lateral projection, and isthmus in posteroanterior and lateral projections. The following calibration methods were examined: (1) a 5Fr pigtail catheter or a 1-cm radio-opaque marker catheter, placed at the level of the anatomic structure, (2) a body surface marker in multiple positions, and (3) a 1 x 1-cm radio-opaque rectilinear grid placed either at the center of the thorax or in an anatomic position. Three independent observers made size estimations. The most accurate method for size estimation, in all anatomic positions and for all box sizes, was the 1-cm radio-opaque marker catheter (mean error </=4%). The surface marker was moderately accurate in the smallest box (mean error 3% to 6%), but had a mean error as high as 33% in the adult-sized box. The 5Fr pigtail angiographic catheter overestimated the size of the structure by 3% to 13% (mean 7%). Intra- and interobserver differences in size estimations were not statistically significant. Among the size calibration methods used during pediatric cardiac catheterizations, catheters with radio-opaque markers within the structure of interest were the most accurate. The use of surface markers in larger patients may introduce significant error, risking a potentially inadequate or adverse outcome from the intervention.

Adolescent↗

PubMed2000

Wire-snare technique with distal flow control for coil occlusion of a modified Blalock-Taussig shunt.

Coil occlusion of Blalock-Taussig shunts has been associated with a high rate of device embolization. We describe a technique consisting of transvenous snaring and exteriorization of a guidewire advanced through a modified left Blalock-Taussig shunt, allowing distal shunt flow control and successful coil occlusion of the shunt. Cathet. Cardiovasc. Intervent. 49:51-54, 2000.

Anastomosis, Surgical↗

PubMed2000

A review of the evaluation of clinical teaching: new perspectives and challenges.

PURPOSE: This article discusses the importance of the process of evaluation of clinical teaching for the individual teacher and for the programme. Measurement principles, including validity, reliability, efficiency and feasibility, and methods to evaluate clinical teaching are reviewed. CONTEXT: Evaluation is usually carried out from the perspective of the learner. This article broadens the evaluation to include the perspectives of the teacher, the patient and the institutional administrators and payers in the health care system and recommends evaluation strategies. RESULTS: Each perspective provides specific feedback on factors or attributes of the clinical teacher's performance in the domains of medical expert, professional, scholar, communicator, collaborator, patient advocate and manager. Teachers should be evaluated in all domains relevant to their teaching objectives; these include knowledge, clinical competence, teaching effectiveness and professional attributes. CONCLUSIONS AND IMPLICATIONS: Using this model of evaluation, a connection can be made between teaching and learning about all the expected roles of a physician. This can form the basis for systematic investigation into the relationship between the quality of teaching and the desired outcomes, the improvement of student learning and the achievement of better health care practice. It is suggested that the extent of effort and resources devoted to evaluation should be commensurate with the value assigned to the evaluation process and its outcomes.

Education, Medical↗

PubMed2000

Clinical teaching: maintaining an educational role for doctors in the new health care environment.

CONTEXT AND OBJECTIVES: Good clinical teaching is central to medical education but there is concern about maintaining this in contemporary, pressured health care environments. This paper aims to demonstrate that good clinical practice is at the heart of good clinical teaching. METHODS: Seven roles are used as a framework for analysing good clinical teaching. The roles are medical expert, communicator, collaborator, manager, advocate, scholar and professional. RESULTS: The analysis of clinical teaching and clinical practice demonstrates that they are closely linked. As experts, clinical teachers are involved in research, information retrieval and sharing of knowledge or teaching. Good communication with trainees, patients and colleagues defines teaching excellence. Clinicians can 'teach' collaboration by acting as role models and by encouraging learners to understand the responsibilities of other health professionals. As managers, clinicians can apply their skills to the effective management of learning resources. Similarly skills as advocates at the individual, community and population level can be passed on in educational encounters. The clinicians' responsibilities as scholars are most readily applied to teaching activities. Clinicians have clear roles in taking scholarly approaches to their practice and demonstrating them to others. CONCLUSION: Good clinical teaching is concerned with providing role models for good practice, making good practice visible and explaining it to trainees. This is the very basis of clinicians as professionals, the seventh role, and should be the foundation for the further development of clinicians as excellent clinical teachers.

Australia↗

PubMed2000

Scholarship in teaching: an imperative for the 21st century.

At some medical schools broader definitions of scholarship have emerged along with corresponding changes in their academic reward systems. Such situations are not common, however. The definition of scholarship generally applied by medical schools is unnecessarily narrow and excludes areas of legitimate academic activity and productivity that are vital to the fulfillment of the school's educational mission. The authors maintain that creative teaching with effectiveness that is rigorously substantiated, educational leadership with results that are demonstrable and broadly felt, and educational methods that advance learners' knowledge are consistent with the traditional definition of scholarship. Faculty whose educational activities fulfill the criteria above are scholars and must be recognized by promotion. The authors specifically address scholarship in education, focusing on teaching and other learning-related activities rather than on educational research, which may be assessed and rewarded using the same forms of evidence as basic science or clinical research. They build on Boyer's work, which provides a vocabulary for discussing the assumptions and values that underlie the roles of faculty as academicians. Next, they apply Glassick et al.'s criteria for judging scholarly work to faculty members' educational activities to establish a basis for recognition and reward consistent with those given for other forms of scholarship. Finally, the authors outline the organizational infrastructure needed to support scholars in education.

Education, Medical↗

PubMed2000

Sequence diversity and genomic organization of vomeronasal receptor genes in the mouse.

The vomeronasal system of mice is thought to be specialized in the detection of pheromones. Two multigene families have been identified that encode proteins with seven putative transmembrane domains and that are expressed selectively in subsets of neurons of the vomeronasal organ. The products of these vomeronasal receptor (Vr) genes are regarded as candidate pheromone receptors. Little is known about their genomic organization and sequence diversity, and only five sequences of mouse V1r coding regions are publicly available. Here, we have begun to characterize systematically the V1r repertoire in the mouse. We isolated 107 bacterial artificial chromosomes (BACs) containing V1r genes from a 129 mouse library. Hybridization experiments indicate that at least 107 V1r-like sequences reside on these BACs. We assembled most of the BACs into six contigs, of which one major contig and one minor contig were characterized in detail. The major contig is 630-860 kb long, encompasses a cluster of 21-48 V1r genes, and contains marker D6Mit227. Sequencing of the coding regions was facilitated by the absence of introns. We determined the sequence of the coding region of 25 possibly functional V1r genes and seven pseudogenes. The functional V1rs can be arranged into three groups; V1rs of one group are novel and substantially divergent from the other V1rs. The genomic and sequence information described here should be useful in defining the biological function of these receptors.

Animals↗

PubMed1999

Atrial septostomy as a bridge to lung transplantation in patients with severe pulmonary hypertension.

Long waiting times for lung transplantation have limited the survival of patients with advanced pulmonary hypertension. Atrial septostomy has been used in this group of patients in an attempt to prolong survival. We evaluated the results of atrial septostomy in 12 patients using the static graded balloon dilation technique. Between December 1990 and May 1998, 10 women and 2 men (ages 13 to 56 years, mean 37 years) underwent atrial septostomy. Nine patients had primary and 3 patents had secondary pulmonary hypertension. Five patients deteriorated despite long-term intravenous prostacyclin infusions. The atrial septum was crossed with a Brockenbrough needle, followed by an 0.035-J exchange wire and progressively larger catheter balloons for atrial septal dilation, until systemic oxygen saturation decreased 5% to 10%. An atrial septal defect was successfully created in each patient. The mean right atrial pressure decreased from 23 to 18 mm Hg and the mean systemic oxygen saturation decreased from 93% to 85%. The mean cardiac index increased from 1.7 to 2.1 L/min/m2 and the mean systemic oxygen transport increased from 268 to 317 ml/min/m2. Complications occurred in 3 patients: transient hypotension during transesophageal echocardiography, a femoral pseudoaneurysm, and a femoral arteriovenous fistula. After septostomy, 6 patients had clinical improvement (resolution of ascites, edema, and no further episodes of syncope); 5 of these 6 patients underwent lung transplantation a mean of 6.1 months after septostomy. Six patients did not have clinical improvement after septostomy. Atrial septostomy improves the hemodynamic status and may be useful as a bridge to lung transplantation in selected patients with pulmonary hypertension.

Adolescent↗

PubMed1999

The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of Escherichia coli, a key transporter in the adaptation to Na+ and H+.

The NhaA Na+/H+ antiporter is the main system responsible for adaptation to Na+ and alkaline pH (in the presence of Na+) in Escherichia coli and many other enteric bacteria. It is under intricate control. At the protein level it is regulated directly by pH, one of its regulatory signals. A pH shift from 7 to 8.5 activates the antiporter and, in a fashion correlated with the activity change, confers a conformation change that, in isolated membrane vesicles, is reflected in the exposure of trypsin-cleavable sites. H225 and G338 are essential for the pH response of NhaA. nhaA transcription is dependent on NhaR, a positive regulator of the LysR family, and is regulated by Na+, the other environmental signal. Na+ affects the NhaR/nhaA interaction directly by changing the footprint of NhaR on nhaA in a pH-dependent fashion. The expression of nhaA is also under global regulation of H-NS. We suggest that the pattern of regulation of nhaA found in E. coli is a paradigm for the response of proteins and genes to H+ and Na+, the most common ions that challenge every cell.

Adaptation, Physiological↗

PubMed1999

Surgical repair of an atrial septal defect in a juvenile Sumatran orangutan (Pongo pygmaeus sumatraensis).

A systolic heart murmur was auscultated in a 2-yr-old female Sumatran orangutan (Pongo pygmaeus sumatraensis) with a slower than expected growth rate. Cardiac ultrasound revealed an 11-mm atrial septal defect. Cardiac catheterization confirmed the diagnosis. Surgical repair was performed during cardiopulmonary bypass using a pericardial patch. The bypass pump was primed with human albumin and donor orangutan whole blood of a compatible type. Hematuria occurred shortly after the initiation of cardiopulmonary bypass. Successful repair was immediately confirmed with transesophageal ultrasonography. The animal was extubated shortly after returning to spontaneous ventilation but had to be reintubated 4 hr later due to tachypnea and decreased SpO2. Additional extubation attempts failed, necessitating continuous positive pressure ventilation, monitoring, and intensive care environment. Thoracic radiographs suggested adult respiratory distress syndrome. The animal required 14 days of intensive care before extubation of the trachea was successful. After 4 wk of isolation, the orangutan was successfully reintroduced to its family group.

Animals↗

PubMed1998

Antisense fosB RNA inhibits thrombin-induced hypertrophy in cultured pulmonary arterial smooth muscle cells.

BACKGROUND: We have previously reported that fosB mRNA is induced by hypertrophic stimuli (thrombin, angiotensin II) but not proliferative stimuli (platelet-derived growth factor, basic fibroblast growth factor) in pulmonary arterial smooth muscle cells (PASMCs) (J Biol Chem. 1994;9:6399-6404). Our aim in the present study was to investigate the potential role of FosB in PASMC hypertrophy. METHODS AND RESULTS: Adenoviruses carrying sense or antisense fosB RNA expression cassettes were used to infect cultured PASMCs with the aim of increasing or inhibiting fosB expression, respectively. We examined whether fosB expression modification affected the growth of quiescent PASMCs, thrombin-induced hypertrophy, or platelet-derived growth factor-induced proliferation. PASMC growth was assessed by daily cell number count, determination of [3H]leucine incorporation, and quantification of total cellular protein. Neither an increase nor a decrease in FosB protein expression caused a significant change in the growth of quiescent PASMCs over a period of 96 hours, indicating that FosB alone is not sufficient to induce hypertrophy. Modification of FosB levels did not affect platelet-derived growth factor-induced PASMC proliferation. An increase in FosB expression did not augment thrombin-induced hypertrophy; however, inhibition of FosB expression resulted in a diminution of thrombin-induced hypertrophy by 58+/-6% (P<0.005). CONCLUSIONS: These results suggest that FosB is necessary but not sufficient for thrombin-induced hypertrophy in cultured PASMCs.

Antisense Elements (Genetics)↗

PubMed1998

Immune mediated and inherited defences against flaviviruses.

BACKGROUND: Flavivirus infection elicits an abundant immune response in the host which is directed against a number of the viral proteins. Resistance to flavivirus-induced disease can also be controlled via a non-immune mechanism involving the product of a naturally occurring murine gene, Flv. OBJECTIVES: To review studies that have reported the mapping of epitopes on flavivirus proteins that elicit T- or B-cell immune responses in mice or humans and to discuss a possible mechanism for flavivirus-specific genetic resistance. STUDY DESIGN: Purified viral proteins and synthetic peptides were used to map B-cell epitopes. Purified proteins, vaccinia-expressed viral protein fragments and synthetic peptides were used to map T-cell epitopes. Congenic-resistant, C3H/RV and congenic susceptible, C3H/He mice and cell cultures were used to study the mechanism of genetic resistance to flavivirus infection. RESULTS: T- and B-cell epitopes have been mapped to the E, NS1 and NS3 proteins of several flaviviruses. Immune responses to the C, PreM, NS2a, NS4a, and NS5 proteins have also been documented. Data suggest that the Flv gene product acts intracellularly to suppress the synthesis of viral genomic RNA. CONCLUSIONS: Although flavivirus infection elicits an abundant immune response, this response is not always rapid enough to protect the host from developing encephalitis. During secondary infections both the humoral and cellular flavivirus-specific responses can confer protection. Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) appear to be caused by an overly vigorous immune response. In genetically resistant animals reduced production of virus results in a slower spread of the infection, which in turn allows time for the immune response to develop and to clear the infection before disease symptoms appear.

Animals↗