Management of Psoriasis Herpeticum in Pregnancy: A Clinical Conundrum.

Introduction. Kaposi varicelliform eruption (KVE) is a widespread cutaneous viral infection, most commonly herpes simplex virus, which affects patients with underlying dermatosis. When KVE occurs in a patient with a history of psoriasis, it is referred to as psoriasis herpeticum, a rare subtype of KVE with only a handful of cases reported in the literature. To the authors' knowledge, we report for the first time a case of psoriasis herpeticum in pregnancy. Case Presentation. A 23-year-old woman in her third pregnancy presented at 26-week gestation with a 10-year history of psoriasis. Cutaneous examination revealed diffuse psoriatic plaques with scattered ~1 cm erosions. Punch biopsy of the skin revealed herpes simplex virus (HSV) infection within a psoriatic plaque, necessitating dermatological treatment. The patient experienced premature rupture of membranes at 37-week gestation. Pelvic exam showed no evidence of herpetic lesions. After labor augmentation, the patient delivered a healthy female infant with no evidence of HSV infection. Discussion. Psoriasis herpeticum is a rare and potentially devastating complication of an underlying dermatosis. With a paucity of data available to guide pregnancy-specific issues, the general management of this condition is controversial and requires a multidisciplinary care approach. Concerns for systemic infection in the mother and vertical transmission to the neonate are of critical importance.

Morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure.

BACKGROUND: Terminal heart failure is associated with chronic myocardial edema, which in part is compensated by increased myocardial lymph flow. However, little is known about the impact of terminal heart failure on lymphangiogenesis. The purpose of the study was to investigate the morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure. METHODS: Paraffin-embedded left ventricular endomyocardial biopsies, taken during heart transplantation from 7 heart transplant recipients (failing heart) and 8 heart transplant donors (control), were investigated by immunohistostaining and triple immunofluorescence for lymphatic endothelial markers LYVE-1, PROX-1, and VEGFR-3. The vessel density was calculated and the ratio of open versus collapsed vessels was estimated by analyzing randomly selected marked vessels. RESULTS: The absolute densities of lymph vessels in failing and control myocardium were not significantly different for all investigated markers. The ratio of open LYVE-1 positive lymph vessels in failing heart was significantly higher than in control (64+/-12.5 vs. 44.3+/-9.3, p<0.008). There was no difference for the ratio of open VEGFR-3 vessels between groups (69.0+/-17.5 vs. 70.7+/-17.2). Triple fluorescent immunohistostaining revealed in failing hearts LYVE-1 and PROX-1 positive open vessels, which were VEGFR-3 negative. VEGFR-3 positive, but LYVE-1 and PROX-1 negative vessels could also be seen. CONCLUSIONS: Myocardial initial lymphatics in patients with terminal heart failure undergo significant morphological changes in comparison to normal hearts. The ratio of open LYVE-1 vessels was higher in failing hearts by no difference in absolute densities for all markers. These findings suggest that appositional growth of initial lymphatics, rather than "de novo" genesis from pluripotent stem cells or sprouting from preexisting venous vessels, may be the predominant mechanism of lymphangiogenesis in terminal heart failure.

Pneumocyte apoptosis induction during cardiopulmonary bypass: effective prevention by radical scavenging using N-acetylcysteine.

Cardiopulmonary bypass (CPB) and cardioplegic arrest are associated with pulmonary dysfunction. We sought to investigate whether pulmonary ischemia/reperfusion during standard CPB and cardioplegic arrest is associated with reactive oxygen species (ROS)-mediated pulmonary tissue injury and pneumocyte apoptosis induction, and whether ROS scavenging using N-acetylcysteine (NAC) attenuates these alterations. Twelve pigs (41 +/- 8 kg) were randomized to receive either NAC (100 mg/kg prior to CPB; n = 7) or placebo (n = 5) and subjected to CPB and 60 min of cold (4 degrees C) crystalloid cardioplegic arrest. We collected lung biopsies prior to CPB, at 60 min CPB, as well as at 30, 60, and 120 min post CPB. Lung specimens were immunocytochemically stained against nitrotyrosine, 8-isoprostaglandin-F(2)alpha, and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) as indicators for ROS-mediated tissue injury and active caspase-3, an apoptosis signal pathway key enzyme. Oxidative stress markers were judged using a scale from 1 to 4 (low to intensive staining), and caspase-3-positive pneumocytes were counted per view field. In placebo, the number of caspase-3-positive pneumocytes significantly increased over time to reach a maximum at 120 min post CPB (p = .03 vs baseline). NAC significantly prevented caspase-3 activation in pneumocytes (p = .001 vs Placebo). Pneumocyte nitrotyrosine and 8-OH-dG staining significantly increased over time (p = .003) in the placebo group, but decreased in the NAC group (p = .004). In both groups staining for 8-isoprostaglandin-F(2)alpha showed no significant changes. This yields the conclusion that standard CPB and cardioplegic arrest initiate ROS-mediated tissue injury and apoptosis in pneumocytes that can be reduced by NAC. Thus, ROS scavenging using NAC may represent a novel approach to minimize lung injury associated with CPB.

Effect of thawing on nitric oxide synthase III and apoptotic markers in cryopreserved human allografts.

BACKGROUND: Previous investigations suggested apoptosis as a contributing factor to early failure of allograft heart valves. As myocardial apoptosis may be induced by nitric oxide (NO) release, this study investigated NO synthase [NOS-III] activation and apoptosis induction in human cryopreserved allografts during the thawing process. METHODS: Frozen myocardial tissue from ten human allograft heart valves, unsuitable for implantation, was submitted to the following conditions: (1) thawing in paraformaldehyde (Control), thawing according to the standard clinical protocol (Standard), standard-thawing with addition of the NOS-inhibitor N-omega-nitro-l-arginine (L-NA; Standard-LNA), and standard thawing with the NOS-stimulator angiotensin II (Standard-AT-II). Cryo-thin sections were investigated by immunostaining for activated NOS-III, cyclic guanosine monophosphate (cGMP), activated caspase-3, and poly-ADP-ribose polymerase (PARP). Quantitative analyses was performed by television densitometry. RESULTS: For activated NOS-III, gray unit values were significantly higher in the Standard and Standard-AT-II group than in the Control and Standard-LNA groups (p < 0.001). Gray unit values for cGMP, a downstream NO-signal-pathway molecule, showed results grossly corresponding to NOS-III activation. Activated caspase-3 and PARP showed high levels of expression in all groups with no significant differences. CONCLUSIONS: Significant activation of NOS-III and subsequent NO-cGMP signal pathway occurs in human cryopreserved allografts during the thawing process and can be significantly reduced by a NOS-III inhibitor administered during thawing. Activation of the apoptosis pathway is also present after thawing, which was not correlated to NOS-III activation. Further experimental investigation focused on the time course and mechanisms of apoptosis and NOS-III activation are required to evaluate NOS and(or) apoptosis inhibitors as therapeutic strategies for improved allograft preservation.

Impact of antioxidative treatment on nuclear factor kappa-B regulation during myocardial ischemia-reperfusion.

Nuclear factor kappa-B (NFkappaB), a transcription factor, plays a role in numerous pathological states such as myocardial ischemia-reperfusion (I/R), apoptosis, and ischemic preconditioning. As both myocardial ischemia and reperfusion (by reactive oxygen intermediates) can activate NFkappaB, we investigated the impact of the antioxidant N-acetylcysteine (NAC) on NFkappaB-regulation in patients subjected to cardioplegic arrest (CA) on cardiopulmonary bypass (CPB). Seventeen coronary artery surgery patients (66+/-9[S.D.] years) subjected to cardiopulmonary bypass (CPB) and cardioplegic arrest were randomized in a double-blind fashion to receive either NAC (100 mg/kg into CPB prime followed by infusion at 20 mg/kg/h; n=9) or placebo (n=8). Transmural LV biopsies were collected prior to CPB (baseline) and at CPB-end and immuno-cytochemically stained against active NFkappaB and phosphorylated IkappaB alpha (activates NFkappaB). At the end of CPB both NFkappaB and IkappaB alpha were unchanged in endothelial cells of controls compared to baseline (45.6+/-7.6 vs. 49.9+/-7.1 and 36.8+/-6.1 vs. 47.5+/-8.6 counts per viewfield (cpv), P>0.05, respectively). In NAC, NFkappaB and IkappaB alpha in endothelial cells were significantly decreased at CPB-end (19.8+/-1.7 vs. 39.1+/-4.1 cpv, P<0.001, and 22.1+/-1.9 vs. 38.3+/-4.4 cpv, P=0.006). In cardiomyocytes, however, there were no changes observed in either group. Antioxidative treatment with NAC decreases NFkappaB-activity following I/R in endothelial cells. We conclude that NFkappaB-activity post I/R is mediated by free radicals rather than ischemia alone.