Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

BACKGROUND: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema. METHODS: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine. RESULTS: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength. CONCLUSION: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.

Racking the brain: detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

PURPOSE The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. MATERIALS AND METHODS The study collective included a total of 109 cases (n=109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. RESULTS Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p<0.001). There was a significant difference (p<0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to white matter ratio was >1.58 when leukoencephalopathy was excluded. CONCLUSIONS Despite normal postmortem changes, generalized brain edema can be differentiated on postmortem computed tomography, and white and gray matter Hounsfield measurements help to determine the cause of death in cases of intoxication or asphyxia. Racking the brain about feasible applications for a precise and reliable brain diagnostic forensic radiology method has just begun.

Acute hemorrhagic edema of young children: a prospective case series.

Acute hemorrhagic edema of young children is a rare leukocytoclastic vasculitis that has been reported exclusively in small retrospective cases series, case reports, or quizzes. Considering that retrospective experience deserves confirmation in at least one observational prospective study, we present our experience with 16 children (12 boys and 4 girls, 5-28 months of age) affected by acute hemorrhagic edema. The patients were in good general conditions and with a low-grade or even absent fever. They presented with non-itching red to purpuric targetoid lesions not changing location within hours, with non-pitting and sometimes tender indurative swelling, and without mucous membrane involvement or scratch marks. Signs for articular, abdominal, or kidney involvement were absent. Antinuclear or antineutrophil cytoplasmic autoantibodies were never detected. The cases were managed symptomatically as outpatients and fully resolved within 4 weeks or less. No recurrence or familiarity was noted. CONCLUSION This is the first prospective evaluation of hemorrhagic edema. Our findings emphasize its distinctive tetrad: a well-appearing child; targetoid lesions that do not change location within hours; non-pitting, sometimes tender edema; complete resolution without recurrence. What is known • Acute hemorrhagic edema of young children is considered a benign vasculitis. • There have been ≈100 cases reported in small retrospective case series. What is new • The first prospective evaluation of this condition emphasizes its features: febrile prodrome; well-appearing child; targetoid lesions not changing location within hours; non-pitting, sometimes tender indurative edema; absent extracutaneous involvement; resolution within 3 weeks. • Antineutrophil cytoplasmic autoantibodies do not play a pathogenic role.

Differentiation of Diabetic Macular Edema From Pseudophakic Cystoid Macular Edema by Spectral-Domain Optical Coherence Tomography.

PURPOSE: To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) based solely on spectral-domain optical coherence tomography (SD-OCT). METHODS: This cross-sectional study included 134 participants: 49 with PCME, 60 with DME, and 25 with diabetic retinopathy (DR) and ME after cataract surgery. First, two unmasked experts classified the 25 DR patients after cataract surgery as either DME, PCME, or mixed-pattern based on SD-OCT and color-fundus photography. Then all 134 patients were divided into two datasets and graded by two masked readers according to a standardized reading-protocol. Accuracy of the masked readers to differentiate the diseases based on SD-OCT parameters was tested. Parallel to the masked readers, a computer-based algorithm was established using support vector machine (SVM) classifiers to automatically differentiate disease entities. RESULTS: The masked readers assigned 92.5% SD-OCT images to the correct clinical diagnose. The classifier-accuracy trained and tested on dataset 1 was 95.8%. The classifier-accuracy trained on dataset 1 and tested on dataset 2 to differentiate PCME from DME was 90.2%. The classifier-accuracy trained and tested on dataset 2 to differentiate all three diseases was 85.5%. In particular, higher central-retinal thickness/retinal-volume ratio, absence of an epiretinal-membrane, and solely inner nuclear layer (INL)-cysts indicated PCME, whereas higher outer nuclear layer (ONL)/INL ratio, the absence of subretinal fluid, presence of hard exudates, microaneurysms, and ganglion cell layer and/or retinal nerve fiber layer cysts strongly favored DME in this model. CONCLUSIONS: Based on the evaluation of SD-OCT, PCME can be differentiated from DME by masked reader evaluation, and by automated analysis, even in DR patients with ME after cataract surgery. The automated classifier may help to independently differentiate these two disease entities and is made publicly available.

RETINAL LAYER RESPONSE TO RANIBIZUMAB DURING TREATMENT OF DIABETIC MACULAR EDEMA: Thinner is Not Always Better.

PURPOSE To identify individual retinal layer thickness changes associated with visual acuity gain in diabetic macular edema treated with ranibizumab using layer segmentation on high-resolution optical coherence tomography scans. METHODS Retrospective observational case series. Thirty-three treatment-naive eyes with diabetic macular edema were imaged by spectral domain optical coherence tomography at monthly visits while receiving intravitreal ranibizumab treatment as needed, guided by visual acuity. Thickness changes of individual layers after 1 year were quantitatively analyzed and correlated with visual acuity gain. RESULTS The mean best-corrected visual acuity improvement at 1 year was 6.2 (SEM ± 1.5) Early Treatment Diabetic Retinopathy Study letters, and central retinal thickness decreased by 66 ± 18 μm. In the central subfield, there was a significant decrease of thickness for all layers (P < 0.05) except the outer nuclear layer. Multiple linear regression analysis revealed that thickness decrease of the inner retina was associated with better visual acuity, whereas for the outer retina the opposite was true. The best estimate of final visual acuity (R = 0.817, P < 0.001) was obtained, by including baseline visual acuity and thickness change of the inner and outer plexiform layers in the model. CONCLUSION Whereas thickness decrease of the inner retina was positively associated with visual acuity gain, the opposite was found for the outer retina. This might be indirect evidence for recovery of the outer retina during ranibizumab treatment.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage.

BACKGROUND Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. METHODS More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. RESULTS Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Δ at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). CONCLUSIONS Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift.

Macular edema in Hispanics with non-insulin dependent diabetes mellitus in Starr County, Texas: Prevalence, incidence and risk factors

This project is based on secondary analyses of data collected in Starr County, Texas from 1981 till 1991 to determine the prevalence, incidence and risk factors for macular edema in Hispanics with non-insulin-dependent diabetes in Starr County, Texas. Two studies were conducted. The first study examined the prevalence of macular edema in this population. Of the 310 diabetics that were included in the study 22 had macular edema. Of these 22 individuals 9 had clinically significant macular edema. Fasting blood glucose was found to be significantly associated with macular edema. For each 10 mg/dl increase in fasting blood glucose there was a 1.07 probability of an increase in the risk of having macular edema. Individuals with fasting blood glucose $\ge$200 mg/dl were found to be more than three times at risk of having macular edema compared to those with fasting blood glucose $<$200 mg/dl.^ In the second study the incidence and the risk factors that could cause macular edema in this Hispanic population were examined. 240 Hispanics with non-insulin-dependent diabetes mellitus and without macular edema were followed for 1223 person-years. During the follow-up period 27 individuals developed macular edema (2.21/100 person-years). High fasting blood glucose and glycosylated hemoglobin were found to be strong and independent risk factors for macular edema. Participants taking insulin were 3.9 times more at risk of developing macular edema compared to those not taking insulin. Systolic blood pressure was significantly related to macular edema, where each 10 mmHg increase in systolic blood pressure was associated with a 1.3 increase in the risk of macular edema.^ In summary, this study suggests that hyperglycemia is the main underlying factor for retinal pathological changes in this diabetic population, and that macular edema probably is not the result of sudden change in the blood glucose level. It also determined that changes in blood pressure, particularly systolic blood pressure, could trigger the development of macular edema.^ Based on the prevalence reported in this study, it is estimated that 35,500 Hispanic diabetics in the US have macular edema. This imposes a major public health challenge particularly in areas with high concentration of Mexican Americans. It also highlights the importance of public health measures directed to Mexican Americans such as health education, improved access to medical care, and periodic and careful ophthalmologic examination by ophthalmologists knowledgeable and experienced in the management of diabetic macular edema. ^

Análisis de la permeabilidad al aire de filtros de protección respiratoria

Los filtros que forman los equipos de protección respiratoria están constituidos por una serie de capas formadas por fibras entrecruzadas, orientadas al azar, que reducen los espacios libres en la dirección del flujo de aire inspiratorio. La estructura tridimensional formada permite orificios mayores que las partículas a retener con el fin de no provocar una excesiva caída de presión. Cuando los orificios se reducen significativamente o se obstruyen por la deposición excesiva de partículas carbón, se crea una elevada resistencia al paso del aire que provoca la incomodidad del filtro, disminuyendo su permeabilidad. Cuanto mayor sea el número de capas filtrantes (espesor) mayor es la eficacia del filtro pero también es mayor la resistencia que ofrece tanto a la respiración como a la eliminación del calor y la humedad generados en su interior.

Excitotoxicity in the lung: N-methyl-D-aspartate-induced, nitric oxide-dependent, pulmonary edema is attenuated by vasoactive intestinal peptide and by inhibitors of poly(ADP-ribose) polymerase.

Excitatory amino acid toxicity, resulting from overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors, is a major mechanism of neuronal cell death in acute and chronic neurological diseases. We have investigated whether excitotoxicity may occur in peripheral organs, causing tissue injury, and report that NMDA receptor activation in perfused, ventilated rat lungs triggered acute injury, marked by increased pressures needed to ventilate and perfuse the lung, and by high-permeability edema. The injury was prevented by competitive NMDA receptor antagonists or by channel-blocker MK-801, and was reduced in the presence of Mg2+. As with NMDA toxicity to central neurons, the lung injury was nitric oxide (NO) dependent: it required L-arginine, was associated with increased production of NO, and was attenuated by either of two NO synthase inhibitors. The neuropeptide vasoactive intestinal peptide and inhibitors of poly(ADP-ribose) polymerase also prevented this injury, but without inhibiting NO synthesis, both acting by inhibiting a toxic action of NO that is critical to tissue injury. The findings indicate that: (i) NMDA receptors exist in the lung (and probably elsewhere outside the central nervous system), (ii) excessive activation of these receptors may provoke acute edematous lung injury as seen in the "adult respiratory distress syndrome," and (iii) this injury can be modulated by blockade of one of three critical steps: NMDA receptor binding, inhibition of NO synthesis, or activation of poly(ADP-ribose) polymerase.

Ultrassonografia vascular comparada à intravascular no diagnóstico das obstruções venosas ilíacas em portadores de insuficiência venosa crônica

Introdução: O tratamento da Insuficiência Venosa Crônica (IVC) é baseado na correção dos refluxos e obstruções ao fluxo sanguíneo venoso. A detecção, a gravidade e o tratamento dessas obstruções venosas, responsáveis pelos sinais e sintomas da IVC, têm sido recentemente estudados e melhor compreendidos. Estes estudos não definem qual o grau de obstrução significativa nem os critérios ultrassonográficos para sua detecção. O objetivo deste estudo foi determinar critérios ultrassonográficos para o diagnóstico das obstruções venosas ilíacas, avaliando a concordância deste método com o ultrassom intravascular (UI) em pacientes portadores de IVC avançada. Métodos: Foram avaliados 15 pacientes (30 membros; 49,4 ± 10,7 anos; 1 homem) com IVC inicial (Classificação Clínica-Etiológica-Anatômica-Physiopatológica - CEAP C1-2) no grupo I (GI) e 51 pacientes (102 membros; 50,53 ± 14,5 anos; 6 homens) com IVC avançada (CEAP C3-6) no grupo II (GII) pareados por sexo, idade e etnia. Todos pacientes foram submetidos à entrevista clínica e à ultrassonografia vascular com Doppler (UV-D), sendo obtidas as medidas de fasicidade de fluxo, os índices de fluxo e velocidades venosas femorais, e as relações de velocidade e de diâmetro da obstrução ilíaca. Foi analisado o escore de refluxo multisegmentar. Os indivíduos do GI foram avaliados por 3 examinadores independentes. Os pacientes do GII foram submetidos ao UI, sendo obtidos a área dos segmentos venosos comprometidos e comparados com os resultados obtidos pelo UV-D, agrupados em 3 categorias: obstruções < 50%; obstruções entre 50-79% e obstruções >= 80%. Resultados: A classe de severidade clinica CEAP predominante no GI foi C1 em 24/30 (80%) membros, e C3 em 54/102 (52,9%) membros no GII. O refluxo foi severo (escore de refluxo multisegmentar >= 3) em 3/30 (10%) membros no grupo I, e em 45/102 (44,1%) membros no grupo II (p<0,001). Houve uma concordância moderadamente elevada entre o UV-D e o UI, quando agrupadas em 3 categorias (K=0,598; p<0,001), e uma concordância elevada quando agrupadas em 2 categorias (obstruções <50% e >= 50%) (K= 0,784; p<0,001). Os melhores pontos de corte e sua correlação com o UI foram: índice de velocidade (0,9; r=-0,634; p<0,001); índice de fluxo (0,7; r=-0,623; p<0,001); relação de obstrução (0,5; r=0,750; p<0,001); relação de velocidade (2,5; r= 0,790; p<0,001); A ausência de fasicidade de fluxo esteve presente em 88,2% dos pacientes com obstrução >=80% ao UV-D. Foi construído um algoritmo ultrassonográfico vascular, utilizando as medidas e os pontos de corte descritos obtendo-se uma acurácia de 79,6% para 3 categorias (K=0,655; p<0,001) e de 86,7% para 2 categorias (k=0,730; p<0,001). Conclusões: O UV-D apresentou uma concordância elevada com o UI na detecção de obstruções >= 50%. A relação de velocidade na obstrução >= 2,5 é o melhor critério para detecção de obstruções venosas significativas em veias ilíacas.