Faculty Bibliography

Sexually-acquired HCV infections among HIV-uninfected men who have sex with men (MSM) have been rare. With the introduction of pre-exposure prophylaxis (PrEP) against HIV, we hypothesized that these infections would increase. Between 2013 and 2018 we diagnosed 15 likely sexually-acquired HCV infections among 14 MSM using PrEP. Most (87%) were asymptomatic, detected by routine ALT or HCV monitoring. Half reported increasing sex partners and drug use after starting PrEP; 5 reported injection of methamphetamine. Interventions are needed to prevent sexually-acquired HCV infections by MSM using PrEP. CDC guidelines for monitoring during PrEP should include regular ALT and HCV testing.

OBJECTIVES: To determine if bilateral transplantation of embryonic mesencephalic dopamine cells into the putamen of patients with PD significantly affected their cognitive functioning when compared with patients receiving sham surgery and to examine the effect of age on cognitive performance after implantation. METHODS: Forty patients (19 women, 21 men; age 34 to 75 years) with idiopathic PD of at least 7 years' duration (mean 14 years) who had disabling motor signs despite optimal drug management were randomly assigned to tissue implants or sham craniotomies in a double-blind design. Neuropsychological tests assessing orientation, attention, language, verbal and visual memory, abstract reasoning, executive function, and visuospatial and construction abilities were administered before and 1 year after surgery. Treatment groups did not differ at baseline in demographic, neuropsychological, motor, depression, or levodopa equivalent measures. RESULTS: Postsurgical change in cognitive performance was not significantly different for real or sham surgery groups. Performance in both groups remained unchanged at follow-up for most measures. CONCLUSIONS: Embryonic dopamine producing neurons can be implanted safely into the putamen bilaterally without impairing cognition in patients with PD, but within the first year, improved cognition should not be expected.

INTRODUCTION/BACKGROUND:Limitations in lesion volume and particularly lesion depth may negatively effect the efficacy of catheter ablation procedures using radiofrequency energy. This study evaluated the safety and efficacy of myocardial ablation using direct intramural injection of ethanol with a novel injection catheter system. METHODS:Left ventricular lesions were performed in 9 male swine (80-85 pounds); two animals were studied 6 weeks following anterior infarction produced by agarose gel embolization. An 8 Fr deflectable catheter equipped with a 27 gauge adjustable depth, retractable needle was directed to the LV using a retrograde aortic approach. Lesion deployment was guided by fluoroscopy and intracardiac echocardiography (ICE). Lesion characteristics were assessed with ICE imaging and pathologic analysis. RESULTS:Ethanol lesions were confined to the tissue directly adjacent to the injection port. Lesions were intramural with no evidence of overlying thrombus. Lesions delivered with a single port injection needle in normal myocardium (n = 24) averaged 1910 +/- 1066 mm(3) with a depth of 8.9 +/- 3.3 mm. Lesions directed to infarct border zones (n = 4) averaged 929 +/- 882 mm(3) with a depth of 4.3 +/- 2.8 mm. Lesions were immediately evident on ICE imaging, and were visualized by increased echo density and tissue swelling. Pathological analysis revealed homogenous lesions with intramural hemorrhage and contraction band necrosis. CONCLUSIONS:Myocardial catheter ablation using direct ethanol injection is feasible, and relatively large and deep intramural lesions can be delivered, even in the infarct border zone. This technique may prove useful in ablation of arrhythmia substrates that are deep to the endocardial surface.

INTRODUCTION/BACKGROUND:Radiofrequency (RF) catheter ablation for ventricular tachycardia (VT) in healed infarction is modestly successful. More extensive, anatomically based procedures and irrigated RF delivery may improve outcome. However, limited data exist regarding the characteristics of irrigated RF lesions in infarcted myocardium. This study addresses this shortcoming. METHODS AND RESULTS/RESULTS:Linear lesions were created at the medial border of a healed anterior infarct in eight pigs using irrigated RF energy guided by sinus rhythm electroanatomic voltage mapping and intracardiac echocardiography (ICE). Lesion morphology and effects on ventricular function were assessed with ICE imaging and pathologic analysis (n = 5). The response to programmed stimulation also was determined before and after linear lesions (n = 6). A mean of 9.4 +/- 1.3 RF applications created linear lesions 37.0 +/- 10.6 mm long, 5 to 12 mm wide, and 4 to 8 mm deep. Thrombus formation was not observed. Lesion delivery resulted acutely in increased local wall thickness at the RF site (26.9% +/- 27.5%; P < 0.0001) and transient systolic dysfunction in adjacent normal myocardium (fractional shortening -38% +/- 34%; P < 0.01). Uniform sustained VT (cycle length 232 +/- 41 msec) was induced in 4 of 6 pigs before ablation, but sustained VT could not be induced afterward. CONCLUSION/CONCLUSIONS:Irrigated RF energy produced relatively large lesions in infarcted myocardium without thrombus formation. Changes in tissue thickness and echo density observed with ICE verify irrigated RF lesion delivery. Temporary left ventricular dysfunction is consistently observed in the normal myocardium adjacent to the linear lesion.

BACKGROUND: Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. METHODS: We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. RESULTS: The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. CONCLUSIONS: Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients.

We prospectively studied 82 men and women with first episodes of genital ulceration. By using newer diagnostic techniques, a definite microbial etiology of 84 infections in 65 of the 82 patients evaluated was found. There were 33 cases of definite primary syphilis, 27 of definite chancroid, and 24 of definite genital herpes simplex. Conclusive evidence of more than one microbial etiology was found for 19 (23%) of the patients. Simultaneous primary syphilis and chancroid was the third most common ulcer infection. This finding underscores the need for both clinical suspicion of multiple infections in patients with genital ulcers and comprehensive testing for all suspicious etiologies

Transthoracic echocardiographic imaging has been difficult to attain in the swine model. This study: (1) compares multiplane transesophageal echocardiography (TEE) with single plane TEE and intracardiac catheter echocardiography (ICE) for imaging of the swine cardiovascular system; and (2) defines normal values using these techniques in a closed chest large swine model (n = 24, body weight 50-114 kg). Multiplane TEE increased success rate over the single plane (the variable plane array only at 0 degrees ) TEE (P < 0.01) for imaging the left ventricular (LV) long-axis view (100% vs 50%), LV outflow tract (100% vs 33%), right atrium and its appendage (79% vs 33%), ascending aorta (100% vs 58%), and aortic arch (100% vs 17%). TEE-derived normal values at end-diastole (ED) and end-systole (ES) were: LV internal diameter (ID) = 49 +/- 3 mm (ED) and 33 +/- 4 mm (ES); LV wall thickness = 7 +/- 1 mm (ED); right ventricular (RV) ID = 24 +/- 4 mm (ED); RV wall thickness = 4 +/- 2 mm (ED); left atrial ID = 48 +/- 6 mm (ES); aortic root ID = 26 +/- 3 mm (ES); LV volume = 157 +/- 49 ml (ED) and 57 +/- 22 ml (ES). Baseline LV ejection fraction (64% +/- 6%), Doppler-derived stroke volume (86 +/- 14 ml), and cardiac index (107 ml/min per kg) were determined. Basal normal values, except for an elevated cardiac index in swine, are comparable to those reported for human adults. Multiplane TEE provided better overall cardiac imaging than did single plane TEE. ICE provided higher resolution imaging of individual cardiac chambers and structures when the ultrasound catheter was introduced into the right or left heart, but whole heart imaging was limited by ultrasound penetration at 12.5 MHz. Normal indices of chamber size and function provide a reference for the physiological significance of induced pathological states in this relevant animal model.

Our previous investigation indicated that, in the 50-114-kg weight range, the swine model provides transeosophageal echocardiographic normal values for cardiac structures comparable to those found in human adults. Intracardiac echocardiographic imaging using a 12.5-MHz ultrasound catheter is limited, due to ultrasonic attenuation. Transesophageal echocardiographic imaging of the right heart is also limited with its anterior anatomic location. To further study the utility of intracardiac imaging, we placed a 5-MHz (30 Fr) multiplane transducer at the junction of the superior vena cava and right atrium, in the right atrium and right ventricle in 8 closed-chest swine (weight 129 +/- 61 kg). In each animal, complete whole heart imaging was obtained, with tomographic views including the cardiac 4-chamber, right atrium, right ventricle and outflow, left atrium and ventricle, and basal great vessels. Major intracardiac anatomic landmarks (i.e., crista terminalis, right atrial appendage, coronary sinus orifice, interatrial septum, tricuspid valve, right ventricular outflow, pulmonary veins, mitral valve and left ventricular papillary muscles) were visualized in every swine. Thus, this 5-MHz multiplane transducer, as a prototype for a steerable low-frequency intracardiac ultrasound catheter, improved both whole heart and individual cardiac structure imaging from a single intracardiac location. Further technological development and refinement is needed for routine use in research and clinical imaging practice.