Perioperative management of patients with congenital or acquired disorders of the QT interval.

QT prolongation can be attributable to various causes that can be categorised as acquired or congenital. Arrhythmias related to QT prolongation can result in clinical presentations, such as syncope and sudden cardiac death. The perioperative period presents a number of issues that may affect a patient's risk of developing polymorphic ventricular tachycardia or torsades de pointes. Although most patients may have an unremarkable perioperative course, some may have complications; this review article aims to help clinicians avoid potential complications, and to help them address treatment for perioperative issues that may occur.

QTc: how long is too long?

Congenital long QT syndrome (LQTS) affects an estimated 1 in 2500 people and typically presents with syncope, seizures or sudden death. Whereas someone exhibiting marked prolongation of the QT interval with QTc exceeding 500 ms who was just externally defibrillated from torsades de pointes while swimming poses negligible diagnostic challenge as to the unequivocal probability of LQTS, the certainty is considerably less for the otherwise asymptomatic person who happens to host a QTc value coined "borderline" (QTc > or = 440 ms). Although a normal QT interval imparts a much lower risk of life-threatening events, it does not preclude a patient from nevertheless harbouring a potentially lethal LQTS-causing genetic mutation. Indeed, genetic testing exerts significant diagnostic, prognostic and therapeutic implications. However, the 12-lead ECG remains the universal initial diagnostic test in the evaluation of LQTS and is subject to miscalculation, misinterpretation and mishandling. This review discusses the components of accurate QTc measurement and diagnosis, re-examines what is known about factors affecting QT interval measurement, and clarifies current recommendations regarding diagnosis of so-called "borderline" QT interval prolongation. The current guideline recommendations for the athlete with LQTS are also summarised.

Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.

BACKGROUND: Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use. PURPOSE: The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully.

Two novel cardiac atrial K+ channels, IK.AA and IK.PC.

Two K(+)-selective channels in neonatal rat atrial cells activated by lipophilic compounds have been characterized in detail. The arachidonic acid-stimulated channel (IK.AA) had a slope conductance of 124 +/- 17 pS at +30 mV in symmetrical 140 mM potassium and a mean open time of approximately 1 ms, and was relatively voltage independent. IK.AA activity was reversibly increased by lowering pH to 6.0. Arachidonic acid was most effective in activating this channel, although a number of lipophilic compounds resulted in activation. Surprisingly, choline, a polar molecule, also activated the channel. A second K+ channel was activated by 10 microM phosphatidylcholine applied to the intracellular surface of inside-out atrial patches. This channel (IK.PC) had a slope conductance of 60 +/- 6 pS at +40 mV and a mean open time of approximately 0.6 ms, and was also relatively voltage independent. Fatty acids are probably monomeric in the membrane under the conditions of our recording; thus detergent effects are unlikely. Since a number of compounds including fatty acids and prostaglandins activated these two channels, an indirect, channel-specific mechanism may account for activation of these two cardiac K+ channels.

Hypotonicity activates a native chloride current in Xenopus oocytes.

Xenopus oocytes are frequently utilized for in vivo expression of cellular proteins, especially ion channel proteins. A thorough understanding of the endogenous conductances and their regulation is paramount for proper characterization of expressed channel proteins. Here we detail a novel chloride current (ICl.swell) responsive to hypotonicity in Xenopus oocytes using the two-electrode voltage clamp technique. Reducing the extracellular osmolarity by 50% elicited a calcium-independent chloride current having an anion conductivity sequence identical with swelling-induced chloride currents observed in epithelial cells. The hypotonicity-activated current was blocked by chloride channel blockers, trivalent lanthanides, and nucleotides. G-protein, cAMP-PKA, and arachidonic acid signaling cascades were not involved in ICl.swell activation. ICl.swell is distinct from both stretch-activated nonselective cation channels and the calcium-activated chloride current in oocytes and may play a critical role in volume regulation in Xenopus oocytes.

Cardiac chloride channels.

Cardiac chloride channels, once largely ignored, are the subject of renewed exploration. Consequently, their molecular identities and electrophysiologic properties are being defined and have revealed a distinct family of ionic channels capable of uniquely influencing the cardiac action potential. Targeting these channel proteins may provide novel antiarrhythmic strategies.

A Standards-Based Architecture Proposal for Integrating Patient mHealth Apps to Electronic Health Record Systems.

BACKGROUND: Mobile health Applications (mHealth Apps) are opening the way to patients' responsible and active involvement with their own healthcare management. However, apart from Apps allowing patient's access to their electronic health records (EHRs), mHealth Apps are currently developed as dedicated "island systems". OBJECTIVE: Although much work has been done on patient's access to EHRs, transfer of information from mHealth Apps to EHR systems is still low. This study proposes a standards-based architecture that can be adopted by mHealth Apps to exchange information with EHRs to support better quality of care. METHODS: Following the definition of requirements for the EHR/mHealth App information exchange recently proposed, and after reviewing current standards, we designed the architecture for EHR/mHealth App integration. Then, as a case study, we modeled a system based on the proposed architecture aimed to support home monitoring for congestive heart failure patients. We simulated such process using, on the EHR side, OpenMRS, an open source longitudinal EHR and, on the mHealth App side, the iOS platform. RESULTS: The integration architecture was based on the bi-directional exchange of standard documents (clinical document architecture rel2 - CDA2). In the process, the clinician "prescribes" the home monitoring procedures by creating a CDA2 prescription in the EHR that is sent, encrypted and de-identified, to the mHealth App to create the monitoring calendar. At the scheduled time, the App alerts the patient to start the monitoring. After the measurements are done, the App generates a structured CDA2-compliant monitoring report and sends it to the EHR, thus avoiding local storage. CONCLUSIONS: The proposed architecture, even if validated only in a simulation environment, represents a step forward in the integration of personal mHealth Apps into the larger health-IT ecosystem, allowing the bi-directional data exchange between patients and healthcare professionals, supporting the patient's engagement in self-management and self-care.

The long QT syndrome: ion channel diseases of the heart.

Once limited to discussions of the Jervell and Lange-Nielsen syndrome and Romano-Ward syndrome, the long QT syndrome (LQTS) is now understood to be a collection of genetically distinct arrhythmogenic cardiovascular disorders resulting from mutations in fundamental cardiac ion channels that orchestrate the action potential of the human heart. Our understanding of this genetic "channelopathy" has increased dramatically from electrocardiographic depictions of marked QT interval prolongation and torsades de pointes and clinical descriptions of people experiencing syncope and sudden death to molecular revelations in the 1990s of perturbed ion channel genes. More than 35 mutations in four cardiac ion channel genes--KVLQT1 (voltage-gated K channel gene causing one of the autosomal dominant forms of LQTS) (LQT1), HERG (human ether-a-go-go related gene.) (LQT2), SCN5A (LQT3), and KCNE1 (minK, LQT5)--have been identified in LQTS. These genes encode ion channels responsible for three of the fundamental ionic currents in the cardiac action potential. These exciting molecular break-throughs have provided new opportunities for translational research with investigations into genotype-phenotype correlations and gene-targeted therapies.

Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome.

OBJECTIVE: To determine the genetic basis for long QT syndrome (LQTS) in a cohort of patients with a personal history or an extended family history of a swimming-triggered cardiac event. PATIENTS AND METHODS: After review of the Mayo Clinic unit medical record system, blood samples or archived autopsy tissue samples were obtained from a retrospective cohort of 35 cases diagnosed as having autosomal dominant LQTS. Exon-specific amplification by polymerase chain reaction and direct sequence analyses were performed on the entire KVLQT1 gene. RESULTS: Six cases had a personal history or an extended family history of a near drowning or drowning. In all 6 cases, LQTS-causing mutations in KVLQT1 gene were identified: 3 deletion mutations, 2 donor splice site mutations, and 1 missense mutation. One of the mutations, a novel donor splicing defect, was determined by postmortem molecular analysis of a paraffin-embedded tissue block from a 12-year-old girl who died in 1976. Distinct KVLQT1 mutations were demonstrated in 3 of the remaining 29 cases. The overall frequency of KVLQT1 defects in LQTS was 100% (6/6) in those with and 10% (3/29) in those without a personal history or an extended family history of drowning or near drowning (P<.001). CONCLUSION: Swimming appears to be a gene-specific (KVLQT1) arrhythmogenic trigger for LQTS. This study provides proof of principle that an unexplained drowning or near drowning may have a genetic basis.

Pulmonary atresia with ventricular septal defect and persistent airway hyperresponsiveness.

OBJECTIVE: We and others have observed significant hyperinflation and airflow obstruction after the surgical repair of pulmonary atresia and ventricular septal defect. This study sought to objectively characterize this problem and determine the prevalence of airway hyperresponsiveness in these patients. METHODS: We performed a prospective study of children and young adults with pulmonary atresia and ventricular septal defect between June 1996 and December 1998. The participants were stratified into 2 distinct molecular genotypes on the basis of chromosome 22q11.2 microdeletion. A clinical diagnosis of asthma and an objective assessment of airway hyperresponsiveness were determined by means of an asthma inventory scale and methacholine challenge testing, respectively. Thirty-three patients were enrolled. Thirteen had velocardiofacial syndrome, each with chromosome 22q11.2 microdeletion. RESULTS: None of the nonsyndromic patients had evidence for haploinsufficiency. Overall, 66.7% (22/33) met criteria for a clinical diagnosis of airway hyperresponsiveness: 62% (8/13) from the microdeletion genotype and 70% (14/20) from the nonsyndromic group. CONCLUSIONS: We have identified an extremely strong association between pulmonary atresia and ventricular septal defect and persistent airway hyperresponsiveness. Haploinsufficiency at chromosome 22q11.2 did not contribute to this predilection for airway hyperresponsiveness. These results provide a basis to anticipate persistent respiratory difficulties after operations in patients with pulmonary atresia and ventricular septal defect. Moreover, this at-risk patient population may yield unique insights into fundamental mechanisms involved in the pathogenesis of airway hyperresponsiveness.

The visible human male: a technical report.

The National Library of Medicine's Visible Human Male data set consists of digital magnetic resonance (MR), computed tomography (CT), and anatomic images derived from a single male cadaver. The data set is 15 gigabytes in size and is available from the National Library of Medicine under a no-cost license agreement. The history of the Visible Human Male cadaver and the methods and technology to produce the data set are described.

SCN5A is expressed in human jejunal circular smooth muscle cells.

Tetrodotoxin-resistant Na+currents are expressed in a variety of muscle cells including human jejunal circular smooth muscle (HJCSM) cells. The aim of this study was to determine the molecular identity of the pore-forming alpha-subunit of the HJCSM Na+ channel. Degenerate primers identified a cDNA fragment of 1.5 kb with 99% nucleotide homology with human cardiac SCN5A. The identified clone was also amplified from single smooth muscle cells by reverse transcriptase-polymerase chain reaction (RT-PCR). Northern blot analysis showed expression of full-length SCN5A. Laser capture microdissection was used to obtain highly purified populations of HJCSM cells. RT-PCR on the harvested cells showed that SCN5A was present in circular but not in longitudinal muscle. A similar result was obtained using a pan-Na+ channel antibody. The full-length sequence for SCN5A was obtained by combining standard polymerase chain reaction with 5' and 3' rapid amplification of cDNA end techniques. The intestinal SCN5A was nearly identical to the cardiac SCN5A. The data indicate that SCN5A is more widely distributed than previously thought and encodes the pore-forming alpha-subunit of the tetrodotoxin-resistant Na+ current in HJCSM cells.

The Visible Human Project: a resource for education.

Throughout recorded history, the relationships between biological structure and function have been central to the understanding of health and disease. For many centuries, the anatomy illustrations originally created during the medieval period formed the basis for the study of medicine. But learning and understanding anatomic structures is limited by the fundamentally two-dimensional images traditionally used to teach them. The digital computer now allows scientists to acquire, store, manipulate, and display complex images. In 1989, the National Library of Medicine (NLM) began a project to use computer technologies to build a prototype digital image library of data representing a complete normal adult human male and female. In this paper, the author describes the beginnings of this project, the Visible Human Project (VHP), the digital images currently available in the VHP database, ongoing research and development, and plans for the future of the VHP.

Characterization of a native swelling-induced chloride current, ICl.swell, and its regulatory protein, pICln, in Xenopus oocytes.

The ability to precisely regulate cell volume is a fundamental property of most cells. Although the phenomenon of regulatory volume decrease (RVD), whereby a swollen cell loses salt and water to restore its original volume, has been appreciated for decades, the molecular identities of the proteins responsible for the volume control machinery and their regulation are essentially unknown. It appears that the rate-determining step in gaining volume control involves the activation of potassium and chloride conductance pathways. We have identified a native chloride current (ICl.swell) responsive to cell swelling in Xenopus oocytes [Ackerman et al. (1994) J Gen Physiol 103: 153-179]. Moreover, we have demonstrated that a cloned protein, pICln, endogenous to oocytes is critical for the activation of this volume-sensitive chloride conductance pathway [Krapivinsky et al. (1994) Cell 76: 439-448]. The identification of an endogenous protein participating in the regulation of an endogenous current may help understand the physiological activities of swelling-induced chloride channels.

New media in medical education.

In 1984 the American Association of Medical Colleges' Panel on the General Professional Education of the Physician challenged the medical community to take a leadership position in the effective application of information science and computer technology to medical education. The medical education community has risen to that challenge through the use of microcomputer technology and optical disc media including the recently developed fully integrated Hypermedia environment to enhance the learning environment.

The Visible Human Project: a resource for anatomical visualization.

The National Library of Medicine (NLM) has long been a world leader in the archiving and distribution of the print-based images of biology and medicine. NLM has also been a pioneer in the use of computer systems to encode and distribute textual knowledge of the life sciences. NLM's Long Range Planning effort of 1985-86 foresaw a coming era where NLM's Bibliographic and factual database services would be complemented by libraries of digital images, distributed over high speed computer networks and by high capacity physical media. The NLM Planning Panel on Electronic Imaging recommended that NLM should undertake the building a digital image library consisting of computerized tomography (CT) and magnetic resonance (MR) images, and cryosection images of a representative, carefully selected and prepared male and female cadaver--the "Visible Human ProjectJ." The male and female Visible Human data sets are now being made available through a license agreement with the NLM. The data sets are supporting a wide range of educational, diagnostic, treatment planning, and commercial uses. The value of this international resource in the public domain increases through its application. Its utility will continue to grow as related databases are attached to it, and as more attributes are given to its image elements.

A new research program in medical image data processing.

The National Library of Medicine, in partnership with the National Institute for Dental and Craniofacial Research, the National Eye Institute, the National Science Foundation, the National Institute for Deafness and Other Communication Disorders, and the National Cancer Institute, has founded a software consortium to support the creation of a public resource in high-dimension data processing tools. The initial emphasis of this effort is to provide public software tools in 3D segmentation and deformable and rigid registration, capable of analyzing the head-and-neck anatomy of the Visible Human Project data. The eventual goal is for the consortium to provide the cornerstone of a self-sustaining software community in 3D, 4D and higher dimensional data analysis. The consortium is committed to open-source code, public software including open interfaces supporting connections to a broad range of visualization and graphic user interface platforms.

From data to knowledge--the Visible Human Project continues.

The U. S. National Library of Medicine (NLM) has long been a world leader in the archiving and distribution of the print-based images of biology and medicine. NLM has also been a pioneer in the use of computer systems to encode and distribute textual knowledge of the life sciences. NLM's Long Range Planning effort of 1985-86 foresaw a coming era where NLM's Bibliographic and factual database services would be complemented by libraries of digital images, distributed over high speed computer networks. The NLM Planning Panel on Electronic Imaging recommended that NLM should undertake the building a digital image library consisting of computerized tomography (CT) and magnetic resonance (MR) images, and cryosection images of a representative, carefully selected and prepared male and female cadaver--the "Visible Human Project ." The male and female Visible Human data sets are now being made available through a license agreement with the NLM. The data sets are supporting a wide range of educational, diagnostic, treatment planning, and commercial uses. The NLM, in partnership with other U.S. government research agencies has begun a three prong effort within the Visible Human Project to address: the creation of a new online, interactive, digital head-and-neck atlas; the development of a tool kit of computational programs capable of automatically performing many of the basic data handling functions required for using Visible Human data in applications; and the improved resolution of future Visible Human data sets through the reduction of the anatomical artifacts introduced by the methods used to stabilize and section the anatomical materials and the development of staining and wide-spectrum methods for increasing tissue contrast.

Anatomic modeling from unstructured samples using variational implicit surfaces.

We describe the use of variational implicit surfaces (level sets of an embedded generating function modeled using radial basis interpolants) in anatomic modeling. This technique allows the practitioner to employ sparsely and unevenly sampled data to represent complex biological surfaces, including data acquired as a series of non-parallel image slices. The method inherently accommodates interpolation across irregular spans. In addition, shapes with arbitrary topology are easily represented without interpolation or aliasing errors arising from discrete sampling. To demonstrate the medical use of variational implicit surfaces, we present the reconstruction of the inner surfaces of blood vessels from a series of endovascular ultrasound images.

An evaluation of the quality of nursing care rendered to patients with intravenous infusions in the Windhoek Hospital Complex.

Patients on intravenous infusions are commonly seen in the Windhoek Hospital Complex. There was concern regarding the type of nursing care these patients received which led to a survey on the quality of care rendered to these patients. The findings showed that care delivered ranged from very poor to good. Some startling information became evident in that legal aspects were often ignored and that basic things such as calculating and charting the daily intake and output, were omitted. Most of these problems can be rectified through in-service education.