Encounter dynamics of a small target by a polymer diffusing in a confined domain.

We study the first passage time for a polymer, that we call the narrow encounter time (NETP), to reach a small target located on the surface of a microdomain. The polymer is modeled as a freely joint chain (beads connected by springs with a resting non zero length) and we use Brownian simulations to study two cases: when (i) any of the monomer or (ii) only one can be absorbed at the target window. Interestingly, we find that in the first case, the NETP is an increasing function of the polymer length until a critical length, after which it decreases. Moreover, in the long polymer regime, we identified an exponential scaling law for the NETP as a function of the polymer length. In the second case, the position of the absorbed monomer along the polymer chain strongly influences the NETP. Our analysis can be applied to estimate the mean first time of a DNA fragment to a small target in the chromatin structure or for mRNA to find a small target.

Assessing the appropriateness of coronary revascularization: the University of Maryland Revascularization Appropriateness Score (RAS) and its comparison to RAND expert panel ratings and American College of Cardiology/American Heart Association guidelines with regard to assigned appropriateness rating and ability to predict outcome.

BACKGROUND: Significant regional variation in procedural frequencies has led to the development of the RAND and American College of Cardiology/American Heart Association (ACC/AHA) guidelines; however, they may be difficult to apply in clinical practice. The University of Maryland Revascularization Appropriateness Score (RAS) was created to address the need for a simplified point scoring system. HYPOTHESIS: The study was undertaken to compare revascularization appropriateness ratings yielded by the RAND Expert Panel Ratings, ACC/AHA guidelines, and the University of Maryland RAS. METHODS: We applied these three revascularization appropriateness scoring systems to 153 catheterization laboratory patients with a variety of cardiac diagnoses and treatments. For each patient, appropriateness scores assigned by each of the three systems were compared with each other and with the actual treatment delivered. Concordance of care with appropriateness score was then correlated with outcome. RESULTS: There were significant differences among all three scoring systems in their ratings and in the concordance of treatment with appropriateness rating. When treatment provided was concordant with RAND ratings, there was a lower occurrence of subsequent coronary artery bypass grafting (CABG), the composite end point of either CABG or percutaneous transluminal coronary angioplasty (PTCA), and the composite end point of death, myocardial infarction (MI), or revascularization. When treatment was concordant with the ACC/AHA guidelines, there was lower occurrence of all-cause mortality, PTCA, the composite end point of either CABG or PTCA, and the composite end point of death, MI, or revascularization. When treatment provided was concordant with the RAS, there was lower occurrence of cardiac death, all-cause death, CABG, the composite end point of either CABG or PTCA, and the composite end point of death, MI, or revascularization. CONCLUSIONS: The RAS is a simple scoring system to assess revascularization appropriateness. When the RAND, ACC/AHA, and RAS systems are compared in a catheterization laboratory population, they rate the same patient differently and vary in their correlation of appropriateness rating with outcome.

A novel deletion at codon 441 of the APC gene associated with ophthalmic lesions (CHRPE) in a South African family.

A novel mutation at codon 441 in exon 10 of the adenomatous polyposis coli (APC) gene was identified in a South African family of mixed ancestry, using a convenient, non-radioactive, heteroduplex-SSCP screening assay. This single thymidine deletion after nucleotide position 1322 creates a frameshift resulting in a downstream stop codon at amino acid residue 453 of the APC gene. Genotypes of nine family members were subsequently correlated with the presence or absence of congenital hypertrophy of the retinal pigment epithelium (CHRPE), since expression of this common extracolonic manifestation of FAP is largely determined by the length of the truncated protein. CHRPE was absent in the five unaffected family members analysed, while four mutation positive subjects showed these ophthalmic lesions. Correlation between the molecular analysis and ophthalmic examinations, performed without knowledge of clinical and genetic status respectively, provided additional evidence in favour of the view that the range of phenotypic expression in FAP may result from different allelic manifestations of APC mutations.

Pulmonary hypertension decreases the predictive accuracy of echocardiographic clues for cardiac tamponade.

A number of echocardiographic clues of pericardial tamponade have been described, but their accuracy in patients with pulmonary hypertension has not been well elucidated. Four echocardiographic clues of pericardial tamponade, namely, right atrial collapse (RAC), right ventricular diastolic collapse (RVDC), marked (> 40%) respiratory variation in transmitral Doppler flow velocity ("flow velocity paradoxus [FVP]"), and inferior vena cava plethora (IVCP) were prospectively evaluated in 32 patients with large pericardial effusions. Of 12 patients with pulmonary hypertension, 6 had invasively determined evidence of tamponade and 6 did not; of 20 patients without pulmonary hypertension, 11 had tamponade and 9 did not. These echocardiographic clues were evaluated in a blinded fashion. Predictive accuracies for RAC, RVDC, FVP, and IVCP were 75%, 80%, 90%, and 95%, respectively, for the patients without pulmonary hypertension and 67%, 58%, 58%, and 83%, respectively, for the patients with pulmonary hypertension. Although all predictive accuracies were lower in patients with pulmonary hypertension, statistically significant decreased predictive accuracy was found only with FVP (p < 0.05). Interestingly, IVCP had the best predictive accuracy among patients with pulmonary hypertension. Our findings suggest that despite somewhat decreased accuracy in patients with pulmonary hypertension, traditional echocardiographic clues for pericardial tamponade may be useful.

Pulmonary sequestration receiving arterial supply from the left circumflex coronary artery.

Pulmonary sequestration is an uncommon anomaly for which the arterial supply is usually derived from the aorta or its major branches. A 66-year-old man is described with a pulmonary sequestration that received its arterial supply from a coronary artery.

Characterization of pulsed-dye laser-mediated vasodilatation in a rabbit femoral artery model of vasoconstriction.

Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation.

Successful use of the right brachial approach to perform directional atherectomy of the left coronary artery.

Although directional coronary atherectomy permits the treatment of complex coronary lesions, its use is limited in patients with peripheral vascular disease by the need to use a large guiding catheter. We describe a patient in whom the right brachial approach was successfully used to perform atherectomy of a semi-protected left main coronary stenosis.

Percutaneous balloon pericardiotomy for the treatment of cardiac tamponade and large pericardial effusions: description of technique and report of the first 50 cases.

OBJECTIVES: This study describes the technique, clinical characteristics and results of the first 50 patients undergoing percutaneous balloon pericardiotomy as part of a multicenter registry. BACKGROUND: Percutaneous balloon pericardiotomy involves the use of a percutaneous balloon dilating catheter to create a nonsurgical pericardial window. METHODS: Patients eligible for percutaneous balloon pericardiotomy had either cardiac tamponade (n = 36) or a moderate to large pericardial effusion (n = 14). In addition to clinical follow-up, serial echocardiograms and chest X-ray films were obtained. RESULTS: The procedure was considered successful in 46 patients after a mean follow-up period of 3.6 +/- 3.3 months. Two patients required an early operation, one for bleeding from a pericardial vessel and one for persistent pericardial catheter drainage. Two patients required a late operation for recurrent tamponade. Minor complications of the procedure included fever in 6 of the first 37 patients (studied before the prophylactic use of antibiotic agents), thoracentesis or chest tube placement in 8 and a small spontaneously resolving pneumothorax in 2. Despite the short-term success of this procedure, the long-term prognosis of the 44 patients with malignant pericardial disease remained poor (mean survival time 3.3 +/- 3.1 months). CONCLUSIONS: Percutaneous balloon pericardiotomy is successful in helping to manage large pericardial effusions, particularly in patients with a malignant condition. It may become the preferred treatment to avoid a more invasive procedure for patients with pericardial effusion and a limited life expectancy.

Ionic contrast agent-mediated endothelial injury causes increased platelet deposition to vascular surfaces.

Contrast agent-mediated endothelial injury may be clinically relevant to the development of acute thrombosis after coronary interventions. We sought to investigate the extent to which contrast agents increase platelet deposition by measuring deposition of indium-111 radiolabeled platelets in an isolated perfused rabbit carotid artery model. Carotid artery segments were perfused at physiologic temperature, pressure, and shear. Vessels were subjected to angioplasty or no angioplasty before exposure to either buffer, diatrizoate (high osmolal/ionic), ioxaglate (low osmolal/ionic), or ioversol (low osmolal/nonionic). Subsequent deposition of indium-111 radiolabeled platelets was quantified. In vessels without balloon angioplasty, platelet deposition (platelets/cm2) was 110,000 +/- 95,000 for buffer perfused vessels, 280,000 +/- 210,000 for vessels perfused with diatrizoate, 290,000 +/- 160,000 for vessels perfused with ioxaglate, and 130,000 +/- 98,000 for vessels perfused with ioversol. After balloon angioplasty, platelet deposition was 1,300,000 +/- 590,000 for buffer controls, 1,800,000 +/- 320,000 for diatrizoate-perfused vessels, 1,500,000 +/- 450,000 for ioxaglate-perfused vessels, and 1,000,000 +/- 180,000 for ioversol-perfused vessels. In vessels without balloon angioplasty, diatrizoate and ioxaglate increased platelet deposition 2.5-fold and 2.6-fold, respectively, relative to buffer-perfused vessels (p < 0.05 and p < 0.01), whereas no increase was seen with ioversol. After balloon angioplasty, diatrizoate increased platelet deposition 1.4-fold over control (p < 0.05), whereas ioxaglate and ioversol showed no statistically significant increase. We conclude that ionic contrast media may cause more endothelial injury and associated localized platelet deposition than nonionic contrast media. These findings may be relevant to coronary interventions, specifically with regard to acute closure and chronic restenosis.

Antegrade selective coronary angiography via the transseptal approach in a patient with severe vascular disease.

We describe a case of a woman with severe vascular disease in whom retrograde access to the aortic root was limited by both aortoiliac and axillary disease. Transseptal catheterization was performed in anticipation of percutaneous aortic valvuloplasty. Selective antegrade angiography was successfully performed using catheters introduced through the transseptal sheath.

Survey of practicing cardiologists in Maryland on their choice of thrombolytic therapy for acute myocardial infarction.

In November 1990, we surveyed 160 practicing community cardiologists in the state of Maryland and 20 academic cardiologists at the University of Maryland Medical Center to determine each individual's preference for aggressive versus nonaggressive therapy for various presentations of acute myocardial infarction. The survey was repeated in April 1991 following a report of the results of the Third International Study of Infarct Survival. All 100 responding cardiologists chose aggressive therapy to manage an early (less than 2 hours) acute anterior myocardial infarction in a 50-year-old patient. However, less aggressive therapy was chosen by many community cardiologists for management of early inferior acute myocardial infarction or for elderly patients. Most community cardiologists chose tissue plasminogen activator as their thrombolytic drug of choice, whereas university cardiologists favored streptokinase. Although there were substantial shifts in choice of thrombolytic agent on the repeat survey, most community physicians still chose tissue plasminogen activator over the less expensive streptokinase.