Echocardiographic evaluation of young adults with nonhemorrhagic cerebral infarction

We reviewed echocardiographic findings in patients aged 15 to 45 years with acute nonhemorrhagic cerebral infarction (NHCI). Among 132 patients with NHCI, 96 (72.7%) had M-mode and two-dimensional echocardiography, including contrast echocardiography with intravenous saline injection when clinically indicated. Echocardiograms were abnormal in 33 patients. Of these, 7 had other conditions that could cause NHCI. Echocardiography corroborated the clinical diagnosis of a cardiogenic source for cerebral infarction in 17 others. The other 9 had no other clues for cardiovascular disease. Potential etiologies of NHCI diagnosed by echocardiography in these 9 cases included: paradoxical embolism, 5 patients; right atrial myxoma, 1; rheumatic mitral valve vegetation, 1; myxomatous mitral valve (marantic endocarditis at postmortem), 1; and left atrial enlargement associated with decreased left ventricular function, 1. Routine echocardiography frequently conveys useful information in patients under age 45 with NHCI. In young patients with cerebral embolism of unknown etiology if routine M-mode and two dimensional echocardiographic studies are normal, contrast echocardiographic studies should be performed to rule out intracardiac shunts and the possibility of paradoxical cerebral embolism.     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

Drug Coated Balloon Is Less Effective for Treatment of DES In‐Stent Restenosis Both in Native Coronary Arteries and Saphenous Vein Grafts: Results From a Bicenter Registry

Background

The paclitaxel drug coated balloon (DCB) is an established treatment for bare metal stent (BMS) in‐stent restenosis (ISR) in native coronary arteries. The evidence of DCB‐application for drug eluting stent (DES) ISR both in native coronaries and saphenous vein grafts (SVG) is limited. Aim of our study was to compare the differential efficacy of DCB for treatment of BMS‐ and DES‐ISR in native coronary vessels and SVGs.

Methods and Results

N = 135 DCB‐treated patients with available follow up (FU) angiography were included in this retrospective study. Patients received treatment between April 2009 and March 2013 at 2 tertiary care hospitals in Germany. DCB was applied in BMS‐ISR (n = 65; 48%) and DES‐ISR (n = 70; 52%). DCB‐treated lesions were located in native coronary arteries (n = 110; 81%; BMS‐ISR: n = 58; 53%; DES‐ISR: n = 52; 47%) and SVGs (n = 25; 19%; BMS‐ISR: n = 7, 28%; DES‐ISR: n = 18, 72%). Median FU was 12 months. Endpoints were binary restenosis and target lesion revascularization (TLR). Binary restenosis (29% vs. 57%; P < 0.01) and TLR (18% vs. 46%; P < 0.01) were significantly more frequent in DES‐ISR versus BMS‐ISR. In SVGs, TLR was required in 72% (DES‐ISR) versus 14% (BMS‐ISR); P = 0.02. In the Kaplan–Meier‐analysis freedom from both endpoints was significantly decreased in the DES‐lesions both in the total population (binary restenosis P < 0.01; TLR P < 0.01) and native coronaries (binary restenosis P = 0.02; TLR P = 0.04).

Conclusions

DCB treatment is less effective in DES‐ISR than in BMS‐ISR. The diminished efficacy of DCB treatment is even more pronounced in DES‐ISR located within degenerated SVGs.

     

Effect of high-dose cyclophosphamide and total-body irradiation on left ventricular function in adult patients with leukemia undergoing allogeneic bone marrow transplantation

Protocols used to prepare patients with leukemia for bone marrow transplantation have the potential for cardiac toxicity due to high-dose cyclophosphamide and total-body irradiation. We have reported one regimen, combining cytarabine (5 mg/kg), cyclophosphamide (90 mg/kg), and total-body irradiation (900 cGy), which is relatively effective in the treatment of leukemia. To assess cardiac effects of this treatment regimen, we performed serial echocardiography and radionuclide ventriculography in 28 patients with leukemia (age range, 18-48 years; mean, 31; 21 males) undergoing allogeneic bone marrow transplantation. No significant change in left ventricular fractional minor axis shortening or increase in left ventricular diastolic dimension was seen with weekly echocardiography. At an average of 77 days (range, 28-358) after transplant, repeat radionuclide ventriculography in 17 patients revealed no significant change in resting left ventricular ejection fraction compared to that on admission to the hospital (58% +/- 6.8% vs 56% +/- 8.0% SD; P = not significant). In seven of these 17 patients (41%), resting ejection fraction fell between baseline and discharge (from mean of 60% to 50%). Resting ejection fraction in four of these patients (23% of the entire group) fell into the abnormal range (from mean of 56% to 44%; lowest, 41%). Ten patients also had exercise radionuclide ventriculography and all had normal responses (greater than 5% increase with exercise) pre- and post-transplant. We conclude that this effective bone marrow transplantation regimen has little apparent short-term cardiac toxicity in the majority of patients; since a few patients do exhibit a deterioration in left ventricular function, continued cardiac surveillance is probably indicated in posttransplant patients.     

Combined transesophageal echocardiography and transesophageal cardioversion probe: technical aspects.

A probe assembly for simultaneous transesophageal echocardiography and transesophageal cardioversion has been developed. This probe allows cardioversion with the delivery of much lower energy than the standard external approach. Details of the probe construction and its use are described, as is the prospect for future practice. The use of a combined probe may be the technique of choice for patients who require both cardioversion and transesophageal echocardiography.