Lidocaine and His bundle extrasystoles. His bundle discharge conducted with functional right of left bundle-branch block, or blocked entirely (concealed).

In this patient, discharge from the bundle of His either conducted normally, conducted with functional right or functional left bundle-branch block, or blocked entirely (concealed), depending on the preceding cycle length and the coupling interval of the premature His bundle depolarization. The presence of both functional right and left bundle-branch block may have been attributable to differences in effective and functional refractory periods between the two bundle branches. Concealed His bundle extrasystoles mimicked first-degree, and types I and II second-degree AV block, according to the interval between His bundle discharge and the subsequent P wave. Lidocaine eliminated His bundle extrasystoles that blocked entirely (concealed) or conducted with functional left bundle-branch block by improving His-Purkinje conduction and by lengthening the coupling interval of the premature His bundle extrasystole. Lidocaine had no effect on AV nodal conduction time. This patient has been known to have concealed His bundle discharge for at least three years and has not required permanent pacemaker insertion.

Early diastolic sound associated with mitral valve prolapse.

A patient with the prolapsing mitral valve syndrome demonstrated a most striking early diastolic sound. Noninvasive study with phonocardiograms, external pulse recordings, and echocardiograms lead us to believe that the sound may be related to the initial opening movement of the mitral valve. To our knowledge, such a mechanism for the production of a diastolic sound has not been previously reported.

"Presystolic" augmentation of diastolic heart sounds in atrial fibrillation.

In the presence of atrial fibrillation, the diastolic murmur of mitral stenosis can appear augmented during early systole before the mitral valve closure sound. This phenomenon has previously been thought to be due to increased blood flow velocity across the narrowing mitral valve orifice. We have observed patients in whom the third heart sound (S3) gallop, the diastolic flow murmur of atrial septal defect and mitral insufficiency and the initial muscular component of the first heart sound become more intense during this period with short, critically timed cycle lengths. This phenomenon appears to be neither peculiar to nor indicative of mitral stenosis and is probably a direct result of the initial muscular contraction of an underfilled ventricle. Either the contraction itself or the sudden deceleration of the rapidly moving flow of blood across the atrioventricular orifice may produce the sound.

An unusual precordial pulse and sound assoicated with large pericardial effusion.

An unusual, high-pitched, early diastolic sound coinciding with a prominent, sharp precordial pulse was observed in a patient with a large chronic pericardial effusion. The pulse and sound coincided exactly with the anterior excursion of the heart within the fluid-filled pericardial sac, suggesting that the sound and pulse result from the ballistic effect of the heart striking the anterior pericardium and chest wall. This finding may be specific for large pericardial effusion with a "swinging heart."

A flexible approach to genome map assembly.

A major goal of the Human Genome Project is to construct detailed physical maps of the human genome. A physical map is an assignment of DNA fragments to their locations on the genome. Complete maps of large genomes require the integration of many kinds of experimental data, each with its own forms of noise and experimental error. To facilitate this integration, we are developing a flexible approach to map assembly based on logic programming and data visualization. Logic programming provides a convenient and mathematically rigorous way of reasoning about data, while data visualization provides layout algorithms for assembling and displaying genome maps. To demonstrate the approach, this paper describes numerous rules for map assembly implemented in a data-visualization system called Hy+. Using these rules, we have successfully assembled contigs (partial maps) from real and simulated mapping data-data that is noisy, imprecise and contradictory. The main advantage of the approach is that it allows a user to rapidly develop, implement and test new rules for genome map assembly, with a minimum of programming effort.

Good maps are straight.

This paper proposes a simplified approach to the assembly of large physical genome maps. The approach focuses on two key problems: (i) the integration of diverse forms of data from numerous sources, and (ii) the detection and removal of errors and anomalies in the data. The approach simplifies map assembly by dividing it into three phases-overlap, linkage and ordering. In the first phase, all forms of overlap data are integrated into a simple abstract structure, called clusters, where each cluster is a set of mutually-overlapping DNA segments. This phase filters out many questionable overlaps in the mapping data. In the second phase, clusters are linked together into a weighted intersection graph. False links between widely separated regions of the genome show up as crooked, branching structures in the graph. Removing these false links produces graphs that are straight, reflecting the linear structure of chromosomes. From these straight graphs, the third phase constructs a physical map. Graph algorithms and graph visualization play key roles in implementing the approach. At present, the approach is at an early stage of development: it has been tested on real and simulated mapping data, and the results look promising. This paper describes the first two phases of the approach in detail, and reports on our progress to date.