Evaluating the clinical and demographic features of extrafacial granuloma faciale.

Granuloma faciale (GF) is an uncommon cutaneous disease of uncertain etiology that predominantly affects the face. Extrafacial lesions are rare. The purpose of this study was to describe the clinical and demographic features of a series of patients with extrafacial manifestations of GF who were diagnosed and treated at a single center over more than 5 decades. We performed a retrospective medical record analysis for all patients diagnosed with extrafacial GF who were treated at Mayo Clinic (Rochester, Minnesota) from 1959 through 2013. During the study period, extrafacial GF was diagnosed in 10 patients (6 men, 4 women), all of whom were white. The mean age was 58.7 years (range, 26-87 years). Seven patients presented with both facial and extrafacial lesions. Although extrafacial lesions are rare in GF, this condition should be included in the differential diagnosis of well-demarcated plaques and nodules found on the arms and legs.

The current literature regarding the cardiovascular effects of electronic cigarettes.

Smoking is the leading cause of preventable morbidity and mortality globally. Electronic cigarettes are marketed both as nicotine substitutes and recreational devices. The popularity of electronic cigarettes has superseded other forms of nicotine replacement therapy. They are also popular in 'never smokers'. This review summarizes the available data regarding the cardiovascular effects of electronic cigarettes. The existing literature is limited and short term with a lack of high-quality studies and adequate follow-up. The available literature suggests that electronic cigarettes have sympathomimetic effects related to nicotine exposure, however, electronic cigarettes also contain other chemicals that require further investigation. Sparse data suggest vascular injury may be another concern. Further research is needed before broad recommendations can be made.

Vascular medicine: aortic and peripheral arterial disease.

The medical management of patients with an abdominal aortic aneurysm (AAA) includes modification of risk factors, smoking cessation, cardiovascular risk treatment, and hypertensive therapy. No specific therapy has been shown to alter disease outcome. Many AAA and thoracic aortic aneurysms are amenable to endovascular treatment. Endovascular repair offers the benefit of shorter hospital stays and lower perioperative morbidity and mortality. Most patients with peripheral arterial disease (PAD) are asymptomatic or have atypical symptoms; only a few present with classic intermittent claudication or critical limb ischemia. Smoking and diabetes mellitus are the most important risk factors for developing PAD.

Coronary artery fistula: single-center experience spanning 17 years.

BACKGROUND: Coronary artery fistula (CAF) is an uncommon form of congenital heart disease. It is often diagnosed incidentally during angiograms. We have reported on clinical characteristics, diagnosis, and management of CAF. METHODS: Retrospective review of a tertiary referral institution's database identified 30 patients with CAF between 1987 and 2004. Mean follow-up was 31.61 +/- 48.03 months. RESULTS: Mean age was 60 +/- 12.7 years. Most common site of CAF origin was the left anterior descending artery (LAD) (14, 46.7%). The most common site of drainage was the main pulmonary artery (15, 50%). Therapeutic strategies were based on symptoms and shunt size. Conservative management was the option in 17 patients (56.7%) with small shunts and mild or no symptoms. Patients with moderate/severe symptoms and/or large shunts were treated with either percutaneous embolization (6, 20%) or surgical ligation (7, 23.3%). Four patients (13.3%) died during follow-up. No deaths were reported in the embolization group, two patients died of cancer in the conservative management group, and two patients died in the surgical group due to cardiac tamponade and cancer, respectively. CONCLUSIONS: Origin of CAF was predominantly from the left system. Clinical presentations were variable depending on type, size of fistula, and the presence of other cardiac conditions. Management of CAF is still controversial and treatment of adult asymptomatic patients with nonsignificant shunting is still a matter of debate. Newer imaging modalities may enhance noninvasive diagnosis. A national registry is necessary for further insights into optimal treatment for large fistulae and the natural history of smaller fistulae.

A case of hemolysis after percutaneous ventricular septal defect closure with a device.

Hemolytic anemia related to intracardiac prosthetic materials has been described. We describe a case of a 74-year-old female with a history of hypertrophic obstructive cardiomyopathy that had a postoperative ventricular septal defect closed with a muscular ventricular septal defect occluder. The device caused intractable hemolytic anemia that required surgical removal and repair. We describe a rare cause of hemolysis complicating transcatheter closure of a post-traumatic ventricular septal defect.

Primary cardiac plasmablastic (diffuse large B-cell) lymphoma mimicking left ventricular aneurysm with mural thrombus.

Primary cardiac lymphoma is rare and is usually of the non-Hodgkin type. By definition, it involves only the heart and the pericardium, with no evidence of extracardiac disease. Primary cardiac lymphoma accounts for 1% of primary cardiac tumors and 0.5% of extranodal lymphomas [Gowda RM, Kahn RA. Clinical perspectives of primary cardiac lymphoma. Angiology 2003;54(5):599-604]. On the other hand, secondary cardiac involvement can occur in approximately 20% of patients with disseminated extracardiac lymphoma [Gowda RM, Kahn RA. Clinical perspectives of primary cardiac lymphoma. Angiology 2003;54(5):599-604]. The majority of primary cardiac lymphomas are diffuse large B-cell lymphomas with centroblastic or immunoblastic cytologic features. Herein, we describe an exceptional case of a primary cardiac plasmablastic variant of diffuse large B-cell lymphoma (Epstein-Barr virus-positive) presenting in an immunocompetent host with chest pain that mimicked a left ventricular apical thrombus.

Surgical treatment of the cardiac manifestations of relapsing polychondritis: overview of 33 patients identified through literature review and the Mayo Clinic records.

OBJECTIVES: To analyze the cardiac findings that necessitate surgery in patients with relapsing polychondritis (RP) and to compare our results to cases in the literature. MATERIAL AND METHODS: A systematic overview of the literature was completed with the addition of cases of RP from the Mayo patient population that necessitated cardiac surgery. RESULTS: Thirty-three patients were identified (25 from the literature and 8 from the Mayo patient population). Nine patients (27%) were female, 22 (67%) were male, and sex was not stated for 2 patients (6%). The patient age ranged from 17 to 69 years (mean +/- SD, 42.5 +/- 15.7 years). At operation, 30 patients (91%) had aortic regurgitation, 21 (64%) had aortic root disease, and 13 (39%) had mitral regurgitation. The most common surgical procedure performed was aortic valve replacement in 12 patients (36%). The most common complications were death in 12 patients (36%) and prosthetic valve dehiscence in 4 patients (12%). CONCLUSIONS: Cardiac involvement is more prominent in the male population and requires more invasive procedures. Aortic valve replacement with composite graft replacement of the ascending aorta along with coronary artery ostial reimplantation should be considered in these patients. Postsurgical valvular complications include prosthetic dehiscence, paravalvular leakage, mediastinitis, and heart failure, and these complications are associated with postoperative corticosteroid therapy. Initiation of second-line immunosuppressive therapy should be substituted for corticosteroids after cardiac surgery.

The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity.

PURPOSE: Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR. METHODS: Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR). RESULTS: Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls. CONCLUSIONS: In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis.

Dynamic left ventricular outflow tract obstruction in senile cardiac amyloidosis.

Dynamic left ventricular outflow tract (LVOT) obstruction is classically seen in hypertrophic obstructive cardiomyopathy (HOCM). This can also be seen in cardiac amyloidosis. We describe a rare case of senile systemic amyloidosis with dynamic LVOT obstruction and concomitant three vessel coronary artery disease presenting with clinical and echocardiographic findings similar to those seen in HOCM. We also highlight the importance of distinguishing the sub-types of amyloidosis so that the appropriate therapy can be offered to patients with cardiac involvement, including coronary artery bypass grafting and septal myotomy/myectomy to relieve LVOT obstruction in the more benign forms of cardiac amyloidosis.

Anti-thyroid methimazole in an acidosis-induced retinopathy rat model of retinopathy of prematurity.

PURPOSE: Methimazole (MMI), an anti-thyroid drug known to reduce serum levels of L-thyroxine (T4) and insulin-like growth factor-1 (IGF-1), has been previously reported to increase the incidence of neovascularization (NV) in an oxygen-induced retinopathy (OIR) model of retinopathy of prematurity (ROP) in rats. We investigated the effect of MMI on the incidence and severity of NV in a non-oxygen-induced model of ROP, acidosis-induced retinopathy (AIR). METHODS: Newborn Sprague Dawley rats were raised in expanded litters of 25 in room air for four or ten days under one of the two following conditions: (1) Our established model of AIR (acidosis via NH4Cl gavage (10 mmol/kg) twice daily from days 2 to 7, followed by two days of recovery) or (2) MMI (given as a 0.1% solution to nursing mothers) in the above AIR model. Left eyes were fixed, and retinas were dissected and ADPase-stained. Flat mounted retinas were graded in a masked manner for presence and severity of NV, and retinal vascular areas were quantified. Serum IGF-1 and T4 concentrations were measured by radioimmunoassay on days 4 and 10. Arterial blood pH measurements were performed on day 4. RESULTS: The incidence and severity of NV were similar between AIR and MMI-AIR rats (incidence: 24% and 33%). Serum IGF-1 concentrations in 10 day MMI-AIR rats were significantly lower than untreated non-acidotic controls (medians: 158 ng/ml and 207 ng/ml; p=0.03). Serum IGF-1 concentrations were similar between 10 day AIR rats and untreated non-acidotic controls (medians: 189 ng/ml and 207 ng/ml; p>0.9). CONCLUSIONS: MMI does not increase the incidence or severity of NV in an AIR neonatal rat model of ROP. Although serum IGF-1 has been considered permissive for NV in immature retinas, supranormal concentrations of serum IGF-1 may not be necessary for abnormal retinal angiogenesis. Further studies are warranted on the roles of serum IGF-1 and L-thyroxine in the pathogenesis of ROP.

The anti-thyroid drug methimazole induces neovascularization in the neonatal rat analogous to ROP.

PURPOSE: To determine the effect of methimazole (MMI), an anti-thyroid drug known to reduce serum l-thyroxine (T4), and insulin-like growth factor (IGF)-1 concentrations, on retinal vascular development in neonatal rats. METHODS: Sprague-Dawley rats (n=175) were raised in expanded litters of 25 in room air and were exposed to MMI from birth (given as a 0.1% solution to nursing mothers for either 4 or 10 days). Experiments ended on day 4 (n=25) or 10 (n=50) of life. A third group was exposed to MMI for the initial 4 days of life and then allowed to recover for the next 6 days (n=50). Fifty control rats were analyzed on day 4 (n=25) or 10 (n=25) of life. Left eyes were fixed, and retinas were dissected and stained with adenosine diphosphatase (ADPase). Retinas were graded for presence and severity of neovascularization (NV) in a masked manner, and retinal vascular areas were quantified. In a subsequent study, serum IGF-1 and T4 levels were measured by radioimmunoassay in an additional 200 rats exposed to treatments identical to those described. RESULTS: Retinal NV occurred in 31% of rats exposed to 10 days of MMI and 4% (P=0.02) of rats exposed to 4 days of MMI, followed by 6 days of recovery. None of the rats exposed to 4 days of MMI alone and none of the control animals was graded positive for NV. Retinal vascular areas were significantly reduced in rats exposed to 4 days of MMI compared with 4-day control animals (36% +/- 6% vs. 50% +/- 6%, P=0.0001). Serum IGF-1 levels were markedly reduced in 4-day MMI rats compared with age-matched control animals (42 ng/mL vs. 133 ng/mL, P=0.0001) and in 10-day MMI rats compared with 10-day control animals (133 ng/mL vs. 206.5 ng/mL, P=0.005). Serum T4 levels were similarly suppressed in the MMI-exposed litters compared with control animals at day 10 (P=0.008). In contrast, rats exposed to 4 days of MMI followed by 6 days of recovery had normal serum IGF-1 and T4 levels by day 10. CONCLUSIONS: The anti-thyroid drug, MMI, induces NV in neonatal rats. This may be mediated by the initial suppression of serum IGF-1. Nevertheless, the lower incidence of NV when serum IGF-1 levels are initially suppressed followed by complete recovery, is contrary to a purely permissive role for serum IGF-1, as reported previously. The relationship between the temporal course of serum IGF-1 and NV in immature retinas needs further investigation.

Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway.

BACKGROUND: Caveolin-1 is a regulator of signaling events originating from plasma membrane microdomains termed caveolae. This study was performed to determine the regulatory role of caveolin-1 on the proliferative events induced by platelet-derived growth factor (PDGF) in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Treatment of VSMCs with PDGF for 24 hours resulted in a loss of caveolin-1 protein expression and plasma membrane-associated caveolae, despite a 3-fold increase in caveolin-1 mRNA. Pretreatment of VSMCs with chloroquine, an inhibitor of lysosomal function, inhibited the PDGF-induced loss of caveolin-1. These studies demonstrated that caveolin-1 was a target of PDGF signaling events. Adenoviral overexpression of caveolin-1 was associated with a switch in PDGF-induced signaling events from a proliferative response to an apoptotic response. This overexpression inhibited PDGF-induced expression of cyclin D1 in the presence of unaffected mitogen-activated protein kinase activation. CONCLUSIONS: Taken together, these studies suggest that caveolin-1 is an inhibitor of PDGF proliferative responses and might be capable of transforming PDGF-induced proliferative signals into death signals.