Molecular Dermatopathology in Malignant Melanoma

At present, immunohistochemistry is taken for granted in the establishment of malignant melanoma (MM) diagnosis. In recent years, molecular diagnosis in dermatopathology has benefited from a vast array of advances in the fields of genomics and proteomics. Sensitive techniques are available for detecting specific DNA and RNA sequences by molecular hybridization. This paper intends to update methods of molecular cytogenetics available as diagnostic adjuncts in the field of MM. Cytogenetics has highlighted the pathogenesis of atypical melanocytic neoplasms with emphasis on the activation of the mitogen-activated protein kinase (MAPK) signalling pathway during the initiation step of the neoplasms. 20 to 40% of MM families have mutations in the tumour suppressor gene p16 or CDKN2A. In addition, somatic mutations in p16, p53, BRAF, and cKIT are present in MM. Genome-wide scan analyses on MM indicate positive associations for genes involved in melanocytic naevi, but MM is likely caused by a variety of common low-penetrance genes. Molecular dermatopathology is expanding, and its use in the assessment of melanocytic neoplasms appears to be promising in the fields of research and diagnosis. Molecular dermatopathology will probably make its way to an increased number of diagnostic laboratories. The expected benefit should improve the patient management. This evolution points to a need for evolution in the training requirements and role of dermatopathologists

Stratification of single-vessel coronary stenosis by ischemic threshold at the onset of wall motion abnormality during continuous monitoring of left ventricular function by semisupine exercise echocardiography.

peer reviewedWe studied the relation between the ischemic threshold at the onset of wall motion abnormality on exercise echocardiography (EE) and the severity of coronary stenosis in patients with 1-vessel coronary artery disease (CAD). We screened 216 consecutive patients who underwent coronary angiography and EE for suspected CAD. Ninety-five (74 men; age, 56 +/- 12 years) satisfied the study criteria, that is, the presence of 1-vessel disease or no evidence of CAD on angiography and a normal baseline echocardiogram. Eighty-seven patients had 1-vessel CAD on angiography, and exercise-induced wall motion abnormality occurred in 73 (77%). Optimal cutoff values of percent diameter stenosis and minimal lumen diameter for predicting a positive EE were 61% (sensitivity and specificity of 76%) and 1.12 mm (sensitivity and specificity of 74%). Among patients with positive EE, heart rate-blood pressure product at ischemic threshold was correlated with quantitative coronary stenosis (r = -0.72, P <.001). The ischemic threshold from continuous monitoring of left ventricular function during semisupine EE is correlated with the severity of coronary stenosis among patients with 1-vessel disease and a normal resting echocardiogram

Dermatitis herpetiforme

ResumenLa dermatitis herpetiforme es una enfermedad autoinmune ampollosa subepid&eacute;rmica caracterizada por una erupci&oacute;n p&aacute;pulo-vesiculosa pruriginosa asociada a dep&oacute;sitos granulares de IgA a nivel de la dermis papilar detectados&nbsp;por IFD. Esta enfermedad en piel se encuentra asociada a una enteropat&iacute;a sensible al gluten la cual es generalmente asintom&aacute;tica.[Armand B, &Aacute;vila MY, Pierard GE, Arrese JE. Dermatitis herpetiforme. MedUNAB 2002; 5(14):75-82].Palabras clave: Dermatitis herpetiforme, IgA granular, dapsona, ampollas subepid&eacute;rmicas

Nutrition and the circadian system

The human circadian system anticipates and adapts to daily environmental changes to optimise behaviour according to time of day and temporally partitions incompatible physiological processes. At the helm of this system is a master clock in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN are primarily synchronised to the 24-h day by the light/dark cycle; however, feeding/fasting cycles are the primary time cues for clocks in peripheral tissues. Aligning feeding/fasting cycles with clock-regulated metabolic changes optimises metabolism, and studies of other animals suggest that feeding at inappropriate times disrupts circadian system organisation, and thereby contributes to adverse metabolic consequences and chronic disease development. ‘High-fat diets’ (HFD) produce particularly deleterious effects on circadian system organisation in rodents by blunting feeding/fasting cycles. Time-of-day-restricted feeding, where food availability is restricted to a period of several hours, offsets many adverse consequences of HFD in these animals; however, further evidence is required to assess whether the same is true in humans. Several nutritional compounds have robust effects on the circadian system. Caffeine, for example, can speed synchronisation to new time zones after jetlag. An appreciation of the circadian system has many implications for nutritional science and may ultimately help reduce the burden of chronic diseases

Circumscribed angiokeratoma. Report of a case and review of the literature

El angioqueratoma circunscrito es el más raro de los angioqueratomas. Aparece desde el nacimiento en las primeras dos décadas de la vida y es más común en mujeres. Generalmente está localizado en piernas y sólo un 10% en miembros superiores, es asintomático. Existen diferencias de opinión encuanto si es una neoplasia o solamente una dilatación de vasos sanguíneos ya existentes. El tratamiento depende del tamaño, profundidad y extensión de la lesión. Se debe considerar la extirpación quirúrgica en la medida en que sea posible. Se describe el caso de un niño de 10 años con cuadro clínico de angioqueratoma circunscrito tratado con crioterapia, con respuesta parcial de las lesiones.[Ávila M, Vásquez AJ, Pierard GE, Arrese JE, Uribe CJ. Angioqueratoma circunscrito. Informe de uncaso y revisión de la literaturaCircumscribed angiokeratoma is the rarest of the angiokeratomas. It appears from birth or in the first two decades of life and is more common in women. It is generally located in the legs and only 10% in the upper limbs, it is asymptomatic. There are differences of opinion as to whether it is a neoplasm or just a dilatation of existing blood vessels. Treatment depends on the size, depth, and extent of the lesion. Surgical removal should be considered whenever possible. The case of a 10-year-old boy with a clinical picture of circumscribed angiokeratoma treated with cryotherapy, with partial response of the lesions, is described. [Ávila M, Vásquez AJ, Pierard GE, Arrese JE, Uribe CJ. Circumscribed angiokeratoma. Report of a case and review of the literatur

Angioqueratoma circunscrito. Informe de un caso y revisión de la literatura

ResumenEl angioqueratoma circunscrito es el m&aacute;s raro de los angioqueratomas. Aperece desde el nacimiento o en las primeras dos d&eacute;cadas de la vida y es m&aacute;s com&uacute;n en mujeres. Generalmente est&aacute; localizado en piernas y un 10% en miembros superiores, es asintom&aacute;tico. Existen diferencias de opini&oacute;n en cuanto si es una neoplasia o solamente una dilataci&oacute;n de vasos sangu&iacute;neos ya existentes. el tratamiento depende del tama&ntilde;o, profundidad y extenci&oacute;n de la lesi&oacute;n. Se debe considerar la extirpaci&oacute;n quir&uacute;rgica en la medida que sea posible. Se describe el caso de un ni&ntilde;o de 10 a&ntilde;os con cuadro cl&iacute;nico de angioqueratoma circunscrito tratado con crioterapia, con respuesta parcial de las lesiones.[&Aacute;vila M, V&aacute;squez AJ, Pierard EG, Arrese JE, Uribe CJ. Angioqueratoma circunscrito. Informe de un caso y revisi&oacute;n de la literatura. MedUNAB 2002;5(14):118-120].Palabras clave: Angioqueratoma, neoplasia de piel, piel

Shrimp Farming Practices in the Puttallam District of Sri Lanka: Implications for Disease Control, Industry Sustainability, and Rural Development

Shrimp farming has great potential to diversify and secure income in rural Sri Lanka, but production has significantly declined in recent years due to civil conflicts, some unsustainable practices and devastating outbreaks of disease. We examined management practices affecting disease prevention and control in the Puttalam district to identify extension services outputs that could support sustainable development of Sri Lankan shrimp farming. A survey on 621 shrimp farms (603 operational and 18 nonoperational) was conducted within the Puttalam district over 42 weeks comprising a series of three-day field visits from August 2008 to October 2009, covering two consecutive shrimp crops. Fundamental deficits in disease control, management, and biosecurity practices were found. Farmers had knowledge of biosecurity but the lack of financial resources was a major impediment to improved disease control. Smallholder farmers were disproportionately constrained in their ability to enact basic biosecurity practices due to their economic status. Basic breaches in biosecurity will keep disease as the rate limiting step in this industry. Plans to support this industry must recognize the socioeconomic reality of rural Sri Lankan aquaculture

Outcomes of Patients with Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics

Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients

Impact of contractile reserve on acute response to cardiac resynchronization therapy

Background: Cardiac resynchronization therapy (CRT) provides benefit for congestive heart failure, but still 30% of patients failed to respond to such therapy. This lack of response may be due to the presence of significant amount of scar or fibrotic tissue at myocardial level. This study sought to investigate the potential impact of myocardial contractile reserve as assessed during exercise echocardiography on acute response following CRT implantation. Methods: Fifty-one consecutive patients with heart failure (LV ejection fraction 27% ± 5%, 67% ischemic cardiomyopathy) underwent exercise Doppler echocardiography before CRT implantation to assess global contractile reserve (improvement in LV ejection fraction) and local contractile reserve in the region of the LV pacing lead (assessed by radial strain using speckle tracking analysis). Responders were defined by an increase in stroke volume ≥15% after CRT. Results: Compared with nonresponders, responders (25 patients) showed a greater exercise-induced increase in LV ejection fraction, a higher degree of mitral regurgitation and a significant extent of LV dyssynchrony. The presence of contractile reserve was directly related to the acute increase in stroke volume (r = 0.48, p<0.001). Baseline myocardial deformation as well as contractile reserve in the LV pacing lead region was greater in responders during exercise than in nonresponders (p<0.0001). Conclusions: Heart failure patients referred to CRT have less chance of improving under therapy if they have no significant mitral regurgitation, no LV dyssynchrony and no contractile myocardial recruitment at exercise