Skin-Related complications of Klippel-Trenaunay Syndrome: a retrospective review of 410 patients.

BACKGROUND: Little is known about skin-related complications in Klippel-Trenaunay syndrome (KTS), a complex vascular anomaly defined by capillary malformation (CM), venous malformation (VM) ± lymphatic malformation (LM) and limb overgrowth. Reported skin-related complications of KTS include ulceration, vascular ectasias (blebs), bleeding and infection. OBJECTIVE: To determine the spectrum, prevalence and predictors of skin-related complications in KTS. METHODS: A retrospective review of 410 patients fulfilling KTS criteria was performed to assess for the presence of skin-related complications. RESULTS: Skin-related complications were present in 45% of patients. Most prevalent were CM-related complications including blebs, bleeding, thickening (25%), cellulitis (22%) and ulceration (21%). Features positively associated with skin-related complications were presence of LM (OR 17.17; P < 0.001), VM on the buttocks/perineum/genitalia (OR 1.92; P = 0.009), CM on the feet (OR 1.77; P = 0.039) and male sex (OR 1.63; P = 0.034). Features negatively associated with skin-related complications were CM on the trunk (OR 0.59; P = 0.029) and tissue hypertrophy of the hands (OR 0.27; P = 0.025). CONCLUSION: Skin-related complications affect nearly half of patients with KTS. Those with lymphatic involvement or malformation presence in the undergarment area or feet are most at risk.

Juvenile idiopathic arthritis and future risk for cardiovascular disease: a multicenter study.

OBJECTIVES: To evaluate the frequency of cardiovascular disease (CVD) and CVD risk factor development in adult patients previously diagnosed with juvenile idiopathic arthritis (JIA). METHOD: A cohort study was conducted utilizing patients at two academic institutions (cohorts 1 and 2). Each institution evaluated the common endpoint of CVD outcomes and CVD risk factor development in adults aged ≥ 30 years and at the 29-year follow-up from disease onset in cohorts 1 and 2, respectively, with comparison to control groups of similar age and sex. RESULTS: Cohort 1 included 41 patients with JIA and follow-up ≥ 30 years of age with comparison to 41 controls. Three patients (7%) had CVD, compared to one control (2%; p = 0.31). Cohort 2 included 170 patients with JIA and a median of 29 years of follow-up from disease onset with comparison to 91 controls. Two patients (2%) had CVD, compared to none of the controls (p = 0.29). The presence of CVD risk factors was found to be increased in the JIA group compared to the controls in three categories: family history of CVD (cohort 1), hypertension (cohort 2), and ever smokers (cohorts 2). CONCLUSIONS: There is no increase in CVD events in patients with JIA 29 years following disease onset when compared to the general population. As these cohorts age, it will be informative to evaluate whether this baseline risk remains present or a trend towards increasing CVD emerges. Continued longitudinal follow-up of these cohorts and larger population-based studies are needed to establish a definitive relationship between JIA and CVD.

Influence of secondary aspiration on human aspiration efficiency.

Computational fluid dynamics (CFD) was used to evaluate the contribution of secondary aspiration to human aspiration efficiency estimates using a humanoid model with realistic facial features. This study applied coefficient of restitution (CoR) values for working-aged human facial skin to the facial regions on the humanoid CFD model. Aspiration efficiencies for particles ranging from 7 to 116 µm were estimated for bounce (allowing for secondary aspiration) and no-bounce (CoR=0) simulations. Fluid simulations used the standard k-epsilon turbulence model over a range of test conditions: three freestream velocities, two breathing modes (mouth and nose breathing, using constant inhalation), three breathing velocities, and five orientations relative to the oncoming wind. Laminar particle trajectory simulations were used to examine inhaled particle transport and estimate aspiration efficiencies. Aspiration efficiency for the realistic CoR simulations, for both mouth- and nose-breathing, decreased with increasing particle size, with aspiration around 50% for 116 µm particles. For the CoR=0 simulations, aspiration decreased more rapidly with increasing particle size and approached zero for 116 µm compared to realistic CoR models (differences ranged from 0% to 80% over the particle sizes and velocity conditions). Differences in aspiration efficiency were larger with increasing particle size (>52 µm) and increased with decreasing freestream velocity and decreasing breathing rate. Secondary aspiration was more important when the humanoid faced the wind, but these contributions to overall aspiration estimates decreased as the humanoid rotated through 90°. There were minimal differences in aspiration between uniform CoR values of 0.5, 0.8, 1.0 and realistic regionally-applied CoR values, indicating differences between mannequin surfaces and between mannequin and human skin will have negligible effect on aspiration for facing-the-wind orientation.

Variability in coefficient of restitution in human facial skin.

BACKGROUND: If particles rebound on human facial skin, they can be re-entrained into the airflow and subsequently inhaled, increasing aspiration efficiency estimates. A realistic estimate of facial skin coefficient of restitution (CoR) is necessary to accurately model particle bounce. This study investigated the effects of sampling location, temperature, humidity levels, age, gender, and BMI on facial skin CoR. METHODS: A torsional ballistometer was used to measure facial CoR for 30 participants divided into three age groups (18-30, 31-40, and 41-65 years), at three temperatures and three humidity levels. The study was repeated twice: once in the late winter and once in the early summer to capture the seasonal variability. RESULTS: The CoR significantly varied across five facial locations, with values ranging from 0.55 to 0.75. Gender, sampling season and the interaction between sampling location and age were found to be significant, but changes in values were relatively small (0.05 at most) and are not considered practically significant. CONCLUSION: CoR was non-uniform across the face. The use of uniform CoR value as modeling input parameters or for mannequin facial surfaces in experimental wind tunnel studies may not be accurate due to the high variability in CoR between facial sampling locations.

The cascading origin of the 2018 Kilauea eruption and implications for future forecasting.

The 2018 summit and flank eruption of Kilauea Volcano was one of the largest volcanic events in Hawai'i in 200 years. Data suggest that a backup in the magma plumbing system at the long-lived Pu'u 'O'o eruption site caused widespread pressurization in the volcano, driving magma into the lower flank. The eruption evolved, and its impact expanded, as a sequence of cascading events, allowing relatively minor changes at Pu'u 'O'o to cause major destruction and historic changes across the volcano. Eruption forecasting is inherently challenging in cascading scenarios where magmatic systems may prime gradually and trigger on small events.

Orthopaedic diagnoses in patients with Klippel-Trenaunay syndrome.

PURPOSE: Klippel-Trenaunay syndrome (KTS) is a rare combined vascular malformation composed of capillary malformation, lymphatic and/or venous malformation and limb overgrowth, which commonly affects the extremities. Due to limb involvement, it is not uncommon for these patients to require referral to an orthopaedic surgeon. Herein we reviewed the prevalence of orthopaedic diagnoses in a large cohort of KTS patients and described the associated surgical interventions. METHODS: Between 1976 and 2012, 410 patients fulfilling strict criteria for KTS were evaluated at a single institution. Patient charts were reviewed for demographic information, details of the clinical evaluation, orthopaedic consultation and surgical interventions. RESULTS: A total of 264 of 410 patients (64%) with confirmed KTS required orthopaedic evaluation. Of these 264 patients, 84% had documented limb-length discrepancy. Other common diagnoses included: angular deformities (10%), scoliosis (9%), osteopenia/osteoporosis (7%), pathological fractures (6%), joint contracture (5%), degenerative joint disease (4%) and limb/joint pain (4%). Of the 264 patients evaluated by orthopaedic surgery, 133 patients (50.4%) underwent 169 surgeries. Surgery was most commonly performed for limb-length discrepancy (62%). Multivariable analysis confirmed an orthopaedic condition was more likely in patients with lymphatic malformation (odds ratio (OR) 3.78; p < 0.001), as well as in those with bone and/or soft-tissue hypertrophy of the lower extremity (OR 7.51; p < 0.001) or foot (OR 3.23; p < 0.001). CONCLUSION: Orthopaedic conditions are common in patients with KTS and approximately 50% require surgical intervention. Those with a lymphatic malformation and/or soft-tissue hypertrophy of the lower extremity are more likely to need surgery. LEVEL OF EVIDENCE: Level IV, Descriptive Case Series.

Cyclic lava effusion during the 2018 eruption of Kilauea Volcano.

Lava flows present a recurring threat to communities on active volcanoes, and volumetric eruption rate is one of the primary factors controlling flow behavior and hazard. The time scales and driving forces of eruption rate variability, however, remain poorly understood. In 2018, a highly destructive eruption occurred on the lower flank of Kilauea Volcano, Hawai'i, where the primary vent exhibited substantial cyclic eruption rates on both short (minutes) and long (tens of hours) time scales. We used multiparameter data to show that the short cycles were driven by shallow outgassing, whereas longer cycles were pressure-driven surges in magma supply triggered by summit caldera collapse events 40 kilometers upslope. The results provide a clear link between eruption rate fluctuations and their driving processes in the magmatic system.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

Expression of the bumetanide-sensitive Na-K-Cl cotransporter BSC2 is differentially regulated by fluid mechanical and inflammatory cytokine stimuli in vascular endothelium.

In vascular endothelium, the electroneutral Na-K-Cl cotransport system is thought to function in the maintenance of a selective permeability barrier in certain vascular beds (e.g., brain), as well as in the preservation of endothelial homeostasis in the face of fluctuating osmotic conditions that may accompany certain pathophysiological conditions (e.g., diabetes mellitus). Here we demonstrate that the gene encoding the bumetanide-sensitive cotransporter BSC2, one of the two major isoforms of Na-K-Cl cotransporters present in mammalian cells, can be differentially regulated by inflammatory cytokines and fluid mechanical forces in cultured endothelium. Interleukin-1beta and tumor necrosis factor-alpha significantly upregulate expression of BSC2 mRNA and protein in human umbilical vein endothelial cells, a response that is inhibited by pretreatment with interferon-gamma. Steady laminar fluid shear stress, at a physiologic magnitude (10 dyn/cm2), is also able to induce and maintain elevated expression of BSC2 in cultured human umbilical vein endothelial cells, while a comparable time-averaged magnitude of turbulent fluid shear stress is not. In vivo, BSC2 mRNA is upregulated after intraperitoneal administration of bacterial endotoxin (LPS) in murine lung and kidney, but not in cardiac tissue. These results provide the first experimental evidence that the BSC2 gene can be selectively regulated by different inflammatory cytokine and fluid mechanical stimuli in endothelium, and support a role for BSC2 in vascular homeostasis and inflammation.

Calcium channel blocking and positive inotropic activities of ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4-aryl-3- pyridine-carboxylate and analogues. Synthesis and structure-activity relationships.

The synthesis and pharmacological evaluation of a series of 2-[(arylsulfonyl)methyl]-4-aryl-5-cyano-1,4-dihydropyridine-3-carboxylic acid esters and analogues are described. These compounds possess a unique profile namely, calcium channel blocking and positive inotropic activities in vitro. Compound 54 was selected as the best compound in the series and was studied in detail. The synthesis and biological profiles of enantiomers of 54 are also reported. The data indicate that although the calcium channel blocking property of 54 is stereospecific the positive inotropic activity is not. Examples of 3- and 6-cyano and other closely related 1,4-dihydropyridine derivatives are described and evaluated for comparison and were found to be devoid of dual activities mentioned above.

Occlusive lesions of cardiac conducting tissue arteries in sudden infant death syndrome.

Cardiac conducting tissue from the hearts of 40 victims of sudden infant death syndrome was examined microscopically by serial section. In five hearts there were marked narrowing of the major artery supplying the atrioventricular node. In another there was similar narrowing of the artery supplying the sinus node. The arterial lesions were focal and characterized by cellular intimal thickening which severely narrowed the vessel lumen. This arterial anomaly may be a contributory factor in the pathogenesis of some cases of sudden infant death.

Pathologic anatomy of Ebstein's anomaly of the heart revisited.

The typical textbook description of Ebstein's anomaly of the heart usually singles out and emphasizes the downward displacement of septal and posterior leaflets of the tricuspid valve. An anatomic reappraisal of this uncommon anomaly suggests that other structural abnormalities of import should be equally stressed. Among the 15 well preserved autopsy specimens in this series, enlargement of the right atrioventricular (A-V) junction and malalignment of the giant and sometimes muscularized anterior leaflet of the tricuspid valve were consistently found. In addition, massive aneurysmal dilation of the right ventricle was present in almost two thirds (9 of 15) of the hearts. Our observations raise the possibility that abnormal embryonic development of the right A-V junction may be the primary event that leads to malformation of the tricuspid valve apparatus.

Surgical significance of the coronary arterial anatomy in truncus arteriosus communis.

In truncus arteriosus communis, as in other anomalies of conotruncal development, the coronary arterial anatomy not only differs from that found in the normal heart but also is subject to unpredictable variations. A consistently distinctive pattern was found in roughly two thirds of 31 cases, a frequency approximating that with which a distinctive coronary arterial pattern occurs in complete transposition of the great vessels. Surgical injury to a major coronary artery was identified in 2 of the 30 hearts from patients with truncus arteriosus communis who died in the early postoperative period. Of particular significance are large branches of the right coronary artery crossing the upper anterior surface of the right ventricle to supply the anterobasal surface of both ventricles and the upper part of the interventricular septum. These arteries are at special risk in surgical procedures utilizing a conduit anastomosed to a right ventriculotomy.

The right ventricular myocardium in Ebstein's anomaly: a morphometric histopathologic study.

Ebstein's anomaly of the tricuspid valve is associated with right ventricular dilatation in approximately two-thirds of cases. Dilatation may be massive. It involves not only the right ventricular wall proximal to the tricuspid valve (atrialized ventricle) but also the right ventricle distal to the valve (funtional right ventricle), including the right ventricular infundibulum. For further definition of the pathogenesis of dilatation of the functional right ventricle (distal chamber), a morphometric histopathologic study was performed on 10 hearts with Ebstein's anomaly and 10 normal age-matched control hearts. In the group with Ebstein's anomaly, five hearts exhibited dilated ventricles and five did not. The study demonstrated that dilatation of the right ventricle in Ebstein's anomaly was associated not only with thinning of the wall but also with an absolute decrease in the number of myocardial fibers counted through the thickness of the wall from endocardium to epidcardium.

Congenital papillary tumor of the tricuspid valve. An unusual cause of right ventricular outflow obstruction in a neonate with trisomy E.

A trisomy E neonate had congenital cardiac anomalies that included a ventricular septal defect, a bicuspid aortic valve, and a congenital papillary tumor of the tricuspid valve. The large papillary tumor was responsible for severe intermittent pulmonary outflow obstruction. The cause and pathogenesis of these rare papillary tumors are unknown, but they are probably related to the more sessile varieties of congenital valvular dysplasia. The life-threatening obstruction to blood flow caused by the congenital valvular tumor probably can be alleviated by simple surgical resection. This type of tumor should be considered in the differential diagnosis of atypical forms of outflow tract obstruction.

Morphologic spectrum of Ebstein's anomaly of the heart: a review.

The rare and curious congenital malformation of the tricuspid valve known as Ebstein's disease or Ebstein's anomaly has been a subject of considerable interest to the cardiologist and the morphologist since its first description by Wilhelm Ebstein in 1866. With the evolution of various surgical techniques for the correction of this anomaly, a thorough understanding of the pathologic anatomy of the malformation assumes greater practical importance. It is now clear that although all hearts with Ebstein's anomaly have in common displaced basal insertions of the septal and posterior leaflets of the tricuspid valve, each case may be pathologically and hemodynamically unique. The malformed tricuspid valve may be incompetent, stenotic, or rarely, imperforate. It may be found in a left-sided tricuspid valve with inversion of ventricles. It is important that these individual variations be recognized so that the operative approach can be tailored to the particular variant of the malformation at hand.

A criss-cross heart. Detailed anatomic description and discussion of morphogenesis.

Hearts with criss-cross atrioventricular connections are rare. Reports in the literature describe great anatomic variations with regard to the atrioventricular connections, spatial relationships of the ventricles, and connections and spatial relationships of the great arteries. In the example described in this report, the basic anatomic picture was that of transposition of the great arteries, but the criss-cross atrioventricular valves had resulted in atrioventricular discordance; hemodynamically, therefore, the situation resembled congenitally corrected transposition. One hypothesis for this anatomic configuration is that pronounced counterclockwise rotation (as viewed from below) brought the ventricular septum into a frontal plane and altered the respective positions of the pulmonary and aortic valves from those usually seen in congenitally corrected transposition and thereby resulted in crossed atrioventricular connections. An alternative hypothesis is that in this case one of the atrioventricular valves (the anteriorly positioned valve) may represent an anomalous communication that developed early in embryogenesis and connected the left atrial appendage to the right ventricular infundibulum.

Vulnerability of coronary arteries in surgery for transposition of the great arteries.

A detailed anatomic study of 82 hearts from patients operated upon for complete or congenitally corrected transposition of the great arteries revealed 12 instances of intraoperative injury to a major coronary artery. Because the coronary arterial anatomy is so variable in transposition of the great arteries, there is a significant risk of injury to them during operation. This is especially so if epicardial adhesions and scarring from previous operations obscure the surface anatomy of the heart. The most common site of injury was adjacent to incisions in the anterior surface of the right-sided ventricle, particularly in congenitally corrected transposition. Without a meticulous examination, these complications of cardiac surgery may be easily overlooked even when the hearts are examined at autopsy.

Anti-inflammatory and lung function effects of montelukast in asthmatic volunteers exposed to sulfur dioxide.

BACKGROUND: Sulfur dioxide (SO(2)) gas may induce acute asthmatic responses when inhaled by individuals in the setting of community or occupational air pollution during exercise. Some asthma medications mitigate the SO(2) response, which is not fully understood but appears to involve multiple mechanisms. OBJECTIVE: We tested the hypothesis that pretreatment with the cysteinyl-leukotriene inhibitor montelukast sodium protects against the inflammatory and bronchoconstrictive effects of SO(2) in the airways of asthmatic subjects. METHODS: Asthmatic volunteers (enrolled, 12 subjects; completed study, 11 subjects) were exposed to 0.75 ppm SO(2) for 10-min periods during exercise (mean ventilation, 35 L/min) and were exposed similarly to filtered air (control condition) after double-blinded pretreatments with montelukast (10 mg/d for 3 days) and placebo. RESULTS: After montelukast pretreatment, specific airways resistance, FEV(1), symptoms, and eosinophil counts in induced sputum showed statistically and clinically significant improvements in preexposure measurements and/or decreased responses to SO(2) exposure or exercise. The mean FEV(1) immediately after exposure was 95% of baseline FEV(1) with montelukast pretreatment vs 82% with placebo. CONCLUSION: Montelukast significantly protects against airways eosinophilic inflammation and bronchoconstriction from SO(2) exposure during exercise. This implies a role for leukotrienes in SO(2)-induced lung effects.

Effect of inhaled salmeterol on sulfur dioxide-induced bronchoconstriction in asthmatic subjects.

UNLABELLED: This study tested the capability of a single 42-microgram dose of inhaled salmeterol xinafoate, a long-acting beta 2-agonist, to protect against bronchoconstrictive effects of exposure to 0.75 ppm sulfur dioxide (SO2) during exercise, for up to 24 h. Ten SO2-responsive adult volunteers with stable asthma were studied under 4 conditions of drug pretreatment/exposure, administered in random order, double-blind: salmeterol/SO2, placebo/SO2, salmeterol/clean air, and placebo/clean air. Each subject underwent 10-min exposure/exercise challenges in a chamber 1, 12, 18, and 24 h after pretreatment. Exercise ventilation rates averaged 29 L/min. Response was measured as the decrement in FEV1 between preexposure and postexposure (lowest value within 30 min). After salmeterol, mean decrement post-SO2 was 7% at 1 h and 12% at 12 h. At 18 and 24 h after salmeterol, and at all times after placebo, mean decrements were 25 to 30%. After 18 and 24 h, salmeterol still improved base-line FEV1 relative to placebo, although improvement was not statistically significant at 24 h. Acute symptom increases accompanied FEV1 decrements. CONCLUSION: In our asthmatic subjects, pretreatment with salmeterol imparted clinically and statistically significant (p < 0.01) protection against bronchoconstriction induced by SO2/exercise for at least 12 h, and maintained an improvement in lung function for as much as 18 h.