Strain delineation and epidemiology of Candida (Clavispora) lusitaniae.

Electrophoretic karyotype (EK) patterns, determined by using contour-clamped homogeneous pulsed-field electrophoresis, and isoenzyme (IZ) profiles were evaluated as methods for strain delineation among 35 isolates of Candida lusitaniae recovered from 15 patients. All isolates were identified to the species level by using conventional morphologic and physiologic criteria, and the identification was confirmed by gas-liquid chromatography analysis of the cellular fatty acids. The isolates were then typed without knowledge of the patient source. The IZ profiles showed all isolates to be closely related. Fifteen EK patterns were found; each pattern was restricted to isolates recovered from a single patient. In contrast, on the basis of heterogeneity in phosphatases, beta-glucosidases, esterases, and catalases, 10 IZ profiles were found; 4 were shared by isolates recovered from more than one patient. Multiple isolates from six patients were analyzed, and for each patient, a single EK- and IZ-defined type was found. The types of isolates obtained from two patients, after the emergence of resistance to amphotericin B, remained the same as the types of isolates obtained earlier. The data suggest that a patient becomes colonized by a single strain of C. lusitaniae which may disseminate to multiple sites, that the colonizing strain can persist during the patient's hospitalization, and that it may develop resistance to amphotericin B. Both EK patterns and IZ profiles can be used to delineate strains of C. lusitaniae, but the EK pattern provides more discriminatory power.     

Potential uses of semiconductor resistance strain gauges in transducers for diagnostic instruments

Biomedical Engineering -     

Simulation of 125I-based radioprobing experiments to study DNA quadruplex structure and topology

Purpose: Certain guanine-rich DNA sequences have the capacity to fold into four-stranded structures stabilized by the stacking of square planar arrangements of four hydrogen-bonded guanine bases. However both the overall topology of folding and the more detailed three dimensional structure of these quadruplexes is difficult to determine or predict, and they can be polymorphic, altering radically depending on environmental conditions. Radioprobing experiments, in which Auger electrons emitted during the decay of a ¹²⁵I-containing base induce strand cleavage in a distance- and structure-dependent manner, have provided possible means of determining these details. Here we have used a combination of computer simulation methods to study the information obtained by one such experiment, reported in 2004.

Method: Models were constructed of three quadruplex topologies considered in the experiment, and one other topology proposed more recently. Molecular Dynamics simulations were used to equilibrate these structures and monitor how they evolved over several nanoseconds in solution. Snapshots from the trajectories were then subjected to Monte Carlo track structure prediction, from which theoretical cleavage patterns have been extracted.

Results: The four topologies were found to yield quite different cleavage patterns, which allow the presence of particular conformations in an experiment to be predicted.

Conclusion: Radioprobing, which is usable in biologically relevant environments, is sensitive enough to distinguish with some confidence between alternative folding topologies in a DNA structure. Monte Carlo track structure simulation can reinforce or question conclusions drawn from experiment, and Molecular Dynamics used with various restraints provides a practical means of guiding a model towards one that yields cleavage patterns closer to those found experimentally.     

Esophageal Aperistalsis and Gastroesophageal Reflux Disorder: Return of Peristalsis after H2-Blocker Therapy

Objectives: Distal esophageal aperistalsis has rarely been reported among patients with gastroesophageal reflux disorder. The purpose of this study, therefore, was to address the frequency with which disorders of peristalsis in general-and distal esophageal aperistalsis in particular-occur in adults with gastroesophageal reflux disorder. Patients and Methods: We studied 314 patients who were referred to our gastrointestinal motility laboratory. On the basis of the endoscopic data, they were divided into three groups: group I, symptomatic patients without endoscopic esophagitis; group II, patients with mild endoscopic esophagitis; and group III. patients with erosive esophagitis. An age-matched group of patients with chest pain unrelated to reflux served as the control. Results: Some form of peristaltic dysfunction was recorded in 56% of the patients with gastroesophageal reflux disorder, significantly more than in the control group ( p < 0.01). A significant correlation existed between the esophageal motor dysfunction scores and the severity of reflux disease. Distal esophageal aperistalsis was present in 3.1% of the reflux groups. There was a correlation between severity of reflux disease and the prevalence of aperistalsis. Aperistalsis occurred in none of the patients in group I, in 3.6% of group II, and in 12.5% of group III ( p < 0.0001). Seven of the patients with aperistalsis who has been treated with H2-blockers were reexamined 4 months later. Return of peristalsis was seen in three of them. Conclusion: Esophageal aperistalsis can be seen in a minority of patients with severe gastroesophageal reflux disorder and is probably a reversible condition.     

Future directions of laser phototherapy for diagnosis and treatment of malignancies: Fantasy,fallacy, or reality?

A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current “fantasies and fallacies” regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.     

Spontaneous vs. naloxone-induced abstinence in dependent rats self-administering L-alpha-acetylmethadol (LAAM) or morphine.

Rats maintained dependence by the self-administration of LAAM or morphine. Following the substitution of saline for LAAM, REM sleep was not disrupted, and the frequency of lever pressing for saline self-injections peaked at about 24 hr. In contrast, following the substitution of saline for morphine, REM sleep was suppressed for 24 hr while the frequency of lever pressing for saline self-injections peaked within 8 hr. When abstinence was induced by hourly iv naloxone injections, REM sleep occurrences were suppressed to a similar degree and for similar durations during naloxone-induced abstinence from both morphine and LAAM. These results suggest that the level of physical dependence maintained during self-administration of LAAM and morphine was similar. The relatively mild abstinence syndrome that was seen during saline substitution in LAAM-dependent rats was most likely related to the long plasma half-lives of the pharmacologically active N-demethylated metabolites of LAAM.     

Off-pump coronary artery grafting in patients with left main coronary artery disease

BACKGROUND: Left main coronary artery disease (LMCD) is considered a relative contraindication to off-pump coronary artery bypass (OPCAB) grafting. This study evaluates the safety and feasibility of OPCAB in these patients compared to an on-pump group (cardiopulmonary bypass, CPB) with LMCD. METHODS: Between January 2000 and July 2002, 95 patients with left main coronary artery stenosis >50% underwent coronary revascularization. Seventy-three unselected patients underwent OPCAB and 22 underwent revascularization using CPB. The techniques used for OPCAB included the use of deep traction sutures in the posterior pericardium and stabilizers to expose the distal coronary targets. Intraluminal coronary shunts were routinely used during construction of the anastomoses. Variables were analyzed using a Student's paired t-test with statistical significance defined as p < 0.05. RESULTS: The mean age in the OPCAB group was 59.9 years and the CPB group 61.8 years (p = 0.54). There were 56 males (77%) in the OPCAB and 18 (82%) in the CPB groups. Mean preoperative left ventricular ejection fraction (LVEF) was 40.3% in OPCAB and 47.3% in CPB (p = 0.015). Average number of grafts was 3.1 in OPCAB and 4.1 in CPB (p = 0.0038). There were no conversions to CPB in those patients initially chosen to undergo OPCAB. There were no early deaths in OPCAB. There was one death in CPB. Mean hospital length of stay was 6.9 days for OPCAB and 9.1 for CPB (p = 0.0159). CONCLUSIONS: Patients with LMCD can undergo OPCAB grafting safely and effectively despite reduced LVEF. LMCD should no longer be seen as a contraindication to perform OPCAB grafting.