Tissue-Toxic Effects of Phosphatidylcholine/Deoxycholate after Subcutaneous Injection for Fat Dissolution in Rats and a Human Volunteer

BACKGROUND The safety of the lipodissolution procedure for the cosmetic treatment of fat is unknown.
OBJECTIVES The objective was to determine the subcutaneous tissue effects of phosphatidylcholine solubilized with deoxycholate (PC/DC) in rats and a human volunteer.
METHODS Rats were treated subcutaneously three times with 50, 300, or 600 μL of PC/DC formula on the abdomen in a chronic study (30 days). A human volunteer undergoing elective liposuction was similarly treated. Cell membrane lysis, cell viability, and histologic status were determined on fresh biopsies of subcutaneous fat from the injection sites.
RESULTS PC/DC dose-dependently reduced membrane integrity and cell viability. Histologic alterations induced by PC/DC included fibroplasia, bandlike fibrosis in the region of the cutaneous muscle, and partial muscle loss. The highest dose caused widespread fat necrosis, fat cyst formation, and necrotic changes of the walls of small blood vessels. Histologic sections of subcutaneous tissue from the human volunteer showed dose-dependent panniculitis, fat cysts, and vessel necrosis. DC (2.5%), tested for comparison in the rat, exerted membrane and histologic effects similar to those of PC/DC. Solvent controls caused negligible alterations.
CONCLUSIONS Injection lipolysis with PC/DC causes tissue fibrosis and necrosis of adipose and vascular tissues in rat and man, making the long-term safety of PC/DC for nonsurgical treatment of subcutaneous fat deposits uncertain.     

Pressure‐Guided Cryoballoon Isolation of the Pulmonary Veins for the Treatment of Paroxysmal Atrial Fibrillation

Pressure‐Guided Cryoballoon Pulmonary Vein Isolation. Background: Pulmonary vein (PV) isolation using a balloon‐mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Complete PV occlusion during balloon ablation has been shown to predict successful electrical isolation. The aim of this study was to correlate mechanical PV occlusion with changes in a pressure curve recorded at the distal tip of the cryoballoon catheter. Methods and Results: We analyzed 51 PVs in 12 patients (61 ± 6 years old) with paroxysmal AF. At first, PV occlusion via the cryoballoon was documented by changes in the pressure curve. Once the PV is occluded, the pressure curve registered in the vein converts from a left atrial pressure curve to a pulmonary artery pressure curve: the PV wedge curve. Occlusion was then confirmed by transesophageal echocardiography (TEE). Following 2 cryoablation applications, electrical PV isolation was assessed with a circumferential mapping catheter. Under the exclusive guidance of changes in the pressure curve at the tip of the cryoballoon, mechanical occlusion confirmed by TEE was achieved in 47 of 51 PVs (92%). Three PVs required further TEE guidance to achieve occlusion. All 50 occluded veins were electrically isolated after cryoablation. One right inferior vein, which could not be occluded with the balloon, displayed conduction post cryoablation and was isolated by focal ablation. Conclusions: Occlusion and electrical isolation of PVs during cryoballoon ablation can be predicted by the appearance of a PV wedge curve at the tip of the catheter. This new straightforward parameter may facilitate the procedure. (J Cardiovasc Electrophysiol, Vol. 21, pp. 120‐125, February 2010)     

IL-12 eliminates the Th-2 dependent protective immune response of mice to larval Strongyloides stercoralis

The goal of the present study was to determine if immune-mediated killing of S. stercoralis L3 in mice could be modulated by shifting from a Th-2 to a Th-1 type immune response. L3 killing in immunized mice was ablated in CD4⁺ T cell-depleted animals, but not in CD8⁺ T cell-depleted or β2-microglobulin-deficient mice. Treatment of immunized mice with IL-4 or IL-5 neutralizing MoAb significantly reduced the protective effects of vaccination against S. stercoralis , while protective immunity was unimpaired in IFN-γ knockout mice. Recombinant IL-12 was administered to infected mice to switch the immune response from a Th-2 to a Th-1 type response. Protective immunity was ablated in immunized mice that received IL-12 therapy. Eosinophil numbers, eosinophil peroxidase levels, and parasite-specific IgG1 levels were lowered in IL-12 treated immunized animals, and parasite-specific IgG2a levels were increased in these animals. The data indicate that eosinophils are important as mediators of larval killing, and that the establishment of Th-2 type immunity results in killing of infective S. stercoralis L3, while a shift to Th-1 type immunity abrogates protective responses.     

Non invasive assessment of regional diastolic left ventricular function with first pass radionuclide functional imaging in ischaemic heart disease

Functional images of regional distribution of rapid filling(RF) rates have been developed and applied at rest and on exercisefor regional analysis of 301 coronary artery territories (103compromised by coronary narrowings, 198 normal). The observedtime-interval of RF averaged 209 ms at rest (range 200 to 280)and 172 ms on exercise (range 125 to 200 ms). Normal RF is directedto the apex, and it is deviated from territories with reducedcompliance to normal territories. Sensitivity in detectionand localization of territories compromised by coronary narrowingsexceeds 90% at rest for the anterior and infero-posterior walland is higher than that obtained from systolic functional images.Specificity amounts also to over 90% and is much higher thanthat observed with systolic functional images. During RF, moderateto severe loss in compliance results in initial regional paradoxicalinward motion in 40 to 45% of anterior or postero-inferior segmentseventually accompanied by significant inward displacement ofblood. Thus, with functional imaging of regional RF rates onecan establish dysfunction and functional significance of coronarynarrowings.     

Transvenous Atrial Cardioversion Threshold in Patients with Implantable Cardioverter Defibrillator: Influence of Active Pectoral Can

Recent studies have shown that transvenous atrial cardioversion is feasible with lead configurations primarily designed for implantable cardioverter defibrillators (ICD). The purpose of this study was to examine the influence of an active pectoral ICD can on the atrial cardioversion threshold (ADFT). Forty consecutive patients received a transvenous single lead system (Endotak DSP 0125, CPI, St. Paul, MN, USA) in combination with a left subpectoral ICD (Ventak Mini, CPI) for treatment of malignant ventricular tachyarrhythmias. Patients were randomized into two groups: 21 received a Hot Can 1743 and 19 patients a Cold Can 1741. Step-down testing of the ventricular defibrillation threshold (VDFT) was performed intraoperatively and evaluation of the ADFT for induced atrial fibrillation (AF) at predischarge. After testing, each patient received a 2-J shock and was asked to quantify discomfort on a numerical scale ranging from 0 to 10. Both groups were comparable with regard to all clinical parameters studied. The mean VDFT in patients with a Hot Can device was significantly lower than in patients with a Cold Can (7.5 ± 2.3 J vs 9.8 ± 3.8 J; P < 0.03). The mean ADFT in the Hot Can group tended to be lower than in the group with Cold Cans (3.4 ± 1.4 J vs 4.5 ± 2.4 J; P = 0.07), and the proportion of patients in whom atrial cardioversion was accomplished at low energies (≤ 3 J) was higher in patients with active compared with patients with inactive pulse generators (57% vs 26%; P < 0.04). The mean discomfort reported after delivery of a 2-J shock was comparable in both groups (Hot Can 5.2 ± 1.9; Cold Can: 5.3 ± 2.1; P = NS). We conclude that the inclusion of an active left subpectoral can in the defibrillation vector of a ventricular ICD seems to reduce the energy requirements for atrial cardioversion without increasing the discomfort caused by low energy shocks.     

Immunity to a challenge infection of Strongyloides stercoralis third-stage larvae in the jird

Jirds support the entire life-cycle of Strongyloides stercoralis. We therefore used this host as a model to define the mechanism of the immune response to a challenge infection, as well as the parasite stage effected by the response. Jirds given a primary infection of S. stercoralis are resistant to re-infection. The use of implanted diffusion chambers containing larvae showed that the immune response killed the third-stage larvae, and this was confirmed by subcutaneous infections. The larvae of a challenge infection are killed within 48 h, a time period too short to allow for the development of L4 and adult worms. The immune response is dependent on both a serum factor and cells, suggestive of an ADCC type response.