Search

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.

In the past two decades there have been substantial advances in understanding the anti-cancer mechanisms of oncolytic viruses (OVs). OVs can mediate their effects directly, by preferentially infecting and killing tumour cells. Additionally, OVs can indirectly generate anti-tumour immune responses. These differing mechanisms have led to a paradoxical divergence in strategies employed to further increase the potency of oncolytic virotherapies. On one hand, the tumour neovasculature is seen as a vital lifeline to the survival of the tumour, leading some to use OVs to target the tumour vasculature in hopes to starve cancers. Therapeutics causing vascular collapse can potentiate tumour hypoxia, nutrient restriction and pro-inflammatory cytokine release, which has shown promise in oncological studies. On the other hand, the same vasculature plays an important role for the dissemination of OVs, trafficking of effector cells and other therapeutics, which has prompted researchers to find ways of normalizing the vasculature to enhance infiltration of leukocytes and delivery of therapeutic agents. This article describes the recent developments of therapies aimed to shut down versus normalize tumour vasculature in order to inform researchers striving to optimize OV-based therapies.

With this operation, it is mainly in view of the removal of the diseased Fallopian tube; the ovary is removed in this case only in those cases, when it is also sick or when it is impossible to separate it from the pipe due to adhesions. This operation differs from a simple ovaryotomy, that with it they always find very abundant adhesions, of varying density and sometimes enormous bleeding when they are separated; fresh adhesions are easily separated, give great bleeding, which by itself soon stops due to vascular collapse; old adhesions are sometimes separated only with tremendous labor, give a slight bleeding, but which does not stop on its own, since the vessels in the thick cicatricial cords do not collapse, and therefore the author combines in the most careful way to chop and bandage them.

This study investigated the impact of temporary vascular collapse on tumour control probability (TCP) in stereotactic body radiotherapy (SBRT), taking into account different radiosensitivities of chronically and acutely hypoxic cells.Three-dimensional tumours with heterogeneous oxygenation were simulated assuming different fractions of collapsed vessels at every treatment fraction. The modelled tumours contained a chronically hypoxic subvolume of 30-60% of the tumour diameter, and a hypoxic fraction ≤5 mm Hg of 30-50%. The rest of the tumours were well-oxygenated at the start of the simulated treatment.For all simulated cases, the largest reduction in TCP from 97% to 2% was found in a tumour with a small chronically hypoxic core treated with 60 Gy in eight fractions and assuming a treatment-induced vascular collapse of 35% in the well-oxygenated region.The timing of SBRT fractions should be considered together with the tumour oxygenation to avoid loss of TCP in SBRT.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a 5-year survival rate of

Smac mimetic compounds (SMCs) are anti-cancer drugs that antagonize Inhibitor of Apoptosis proteins, which consequently sensitize cancer cells to death in the presence of proinflammatory ligands such as tumor necrosis factor alpha (TNF-α). SMCs synergize with the attenuated oncolytic vesicular stomatitis virus (VSVΔ51) by eliciting an innate immune response, which is dependent on the endogenous production of TNF-α and type I interferon. To improve on this SMC-mediated synergistic response, we generated TNF-α-armed VSVΔ51 to produce elevated levels of this death ligand. Due to ectopic expression of TNF-α from infected cells, a lower viral dose of TNF-α-armed VSVΔ51 combined with treatment of the SMC LCL161 was sufficient to improve the survival rate compared to LCL161 and unarmed VSVΔ51 co-therapy. This improved response is attributed to a bystander effect whereby the spread of TNF-α from infected cells leads to the death of uninfected cells in the presence of LCL161. In addition, the treatments induced vascular collapse in solid tumors with a concomitant increase of tumor cell death, revealing another mechanism by which cytokine-armed VSVΔ51 in combination with LCL161 can kill tumor cells. Our studies demonstrate the potential for cytokine-engineered oncolytic virus and SMCs as a new combination immunotherapy for cancer treatment. Keywords: Smac mimetics, tumor necrosis factor alpha, TNF-α, vesicular stomatitis virus, VSV, oncolytic virus, vascular collapse, Smac mimetic compound, SMC, cellular inhibitor of apoptosis 1/2, cIAP1/cIAP2, cancer, immunotherapy

The tumor vasculature with unique characteristics offers an attractive target for anti-cancer therapy. Herein, we put forward a novel antitumor therapeutic mechanism based on the gadofullerene nanocrystals (GFNCs), the agent we have previously shown to efficiently disrupt tumor vasculature by size-expansion with assistance of radiofrequency (RF). However, the tumor vascular disrupting mechanism of RF-assisted GFNCs treatment was not further studied. In the present work, a rapid tumor blood flow shutdown has been observed by the vascular perfusion imaging in vivo and vascular damages were evident 6 h after the RF-assisted GFNCs treatment. Importantly, a significant down-expression of tumor vascular endothelial cadherin (VE-cadherin) treated by RF-assisted GFNCs was further investigated, which caused vascular collapse, blood flow shut-down and subsequent tumor hemorrhagic necrosis. These findings set forth a systematic mechanism on the superior anti-tumor efficiency by RF-assisted GFNCs treatment.

In Sheehan;s syndrome hypopituitarism is caused by the ischemic damage to the pituitary following postpartum hemorrhage and vascular collapse. In Sheehan;s syndrome secondary hypothyroidism occurs. We report here a case of partial Sheehan’s syndrome with primary hypothyroidism with high anti thyroid antibody titre which is an uncommon association.J MEDICINE July 2017; 18 (2) : 115-118

Este síndrome que se ha denominado Nefrosis del Nefrón Distal a Enfermedad Tubular Aguda reconoce en general 3 grandes mecanismos fisiopatológicos en su desarrollo clínico: 1) Destrucción tisular o sanguínea con liberación de elementos nefrotóxicos. 2) Colapso vascular con hipotensión prograsiva y alteraciones arteriales, metabólicas y de los electroitos. 3) Sensibilidad o sensibilización de ciertos parénquimas y de manera preferente del riñón a diversas noxas del metabolismo alterado o a toxinas microbianas o a ciertos compuestos químicos y drogas.

Biological cancer therapies, such as oncolytic, or replication-selective viruses have advantages over traditional therapeutics as they can employ multiple different mechanisms to target and destroy cancers (including direct cell lysis, immune activation and vascular collapse). This has led to their rapid recent clinical development. However this also makes their pre-clinical and clinical study complex, as many parameters may affect their therapeutic potential and so defining reason for treatment failure or approaches that might enhance their therapeutic activity can be complicated. The ability to non-invasively image viral gene expression in vivo both in pre-clinical models and during clinical testing will considerably enhance the speed of oncolytic virus development as well as increasing the level and type of useful data produced from these studies. Further, subsequent to future clinical approval, imaging of reporter gene expression might be used to evaluate the likelihood of response to oncolytic viral therapy prior to changes in tumor burden. Here different reporter genes used in conjunction with oncolytic viral therapy are described, along with the imaging modalities used to measure their expression, while their applications both in pre-clinical and clinical testing are discussed. Possible future applications for reporter gene expression from oncolytic viruses in the phenotyping of tumors and the personalizing of treatment regimens are also discussed.

Clinical observations suggest that the assumption of a linear relationship between chest compression pressure and cardiac output may be oversimplified. More complex behaviour may occur when the transmural pressure is large, changing the compliances and resistances in the intra-thoracic vasculature. A fundamental understanding of these compression induced phenomena is required for improving CPR. An extensively used, lumped element computer model (model I) of the circulation was upgraded and refined to include the intrathoracic vasculature (model II). After validation, model II was extended by adding variable compliances and resistances (model III) to the vascular structures. Successively, ranges of compression pressures, frequencies, duty cycles and compression pulse shapes were applied while controlling all other parameters. Cardiac output was then compared. The nonlinearities in compliance and resistance become important, limiting factors in cardiac output, starting in our experimental series at 70 mmHg peak compression pressure, and increasing with higher pressures. This effect is reproducible for sinusoidal and trapezoidal compression forms, resulting in lower cardiac output in all experiments at high compression pressures. Duty cycle and wait time are key parameters for cardiac output. Our data strongly indicate that vascular compliance, especially the ability of vessels to collapse (and potentially the cardiac chambers), can be a central factor in the limited output generated by chest compressions. Just pushing 'harder' or 'faster' is not always better, as an 'optimal' force and frequency may exist. Overly forceful compression can limit blood flow by restricting filling or depleting volume in the cardiac chambers and central great vessels.

The hereditary disorders of connective tissues (HDCTs) encompass a spectrum of conditions linked pathophysiologically by abnormalities of collagen, fibrillin, and matrix proteins. The clinical picture ranges from morbidity because of musculoskeletal, skin, ocular and visceral pathologies to mortality from acute vascular collapse. For many of the conditions, there is a considerable overlap in clinical features, although severity varies; appreciating the subtle differences in presentation is vital to the clinician in determining the diagnosis. Though conditions associated with severe vascular pathology are rare, other hereditary disorders of connective tissues such as the joint hypermobility syndrome and Stickler's disease are common and probably underrecognized. Abnormal skin elasticity and scaring, joint hypermobility, and chronic arthralgia are important clues that should trigger the clinician to search for underlying hereditary disorders of connective tissues. In this article, we discuss the spectrum of clinical findings, management, and genetic screening of the more common hereditary disorders of connective tissues, highlighting their diagnostic criteria and their differences.

Este estudo mostra os dados da epidemia de dengue e febre hemorrágica da dengue ocorrida na Cidade do Recife no ano de 2002 e as características clínicas, laboratoriais e de necropsia dos 14 casos de óbito por dengue. Foram notificados 35.597 casos, dos quais 208 foram febre hemorrágica da dengue e 14 evoluíram para óbito. O sorotipo Den-3 ocorreu em 76,3% dos casos. A maioria dos óbitos ocorreu entre homens com mais de 20 anos, no 11º dia da doença, assistidos nos hospitais privados. Os valores médios do hematócrito e das plaquetas foram 40,7% e 56.313p/mm³, respectivamente. A hepatite, com níveis elevados de transaminases, ocorreu na maioria dos pacientes, que geralmente encontravam-se anictéricos. Dos quatorze casos, 13 tiveram confirmação laboratorial. Em oito casos o óbito decorreu de fenômenos hemorrágicos, entretanto, nos outros seis casos não foram identificados sangramentos significativos. O choque, decorrente do extravasamento vascular, associado ou não a sangramentos significativos, esteve presente em 12 (85,7%) casos, sendo portanto a principal causa de óbito nos casos graves de dengue.

The experimentally-observed phenomenon of vascular collapse in tumors represents a significant barrier to the delivery of blood-borne therapeutic drugs, and has been attributed to the elevated tissue stresses resulting from confined proliferation of tumor cells. This paper presents a mathematical framework which describes the evolution of growth-induced stresses in tumors and gives new insights into both vascular collapse and tumor growth dynamics. The linear-elastic description of anisotropic growth adopted here provides the mechanical model with a realistic constitutive basis, incorporating both the solid and stress-relaxation characteristics of soft biological tissues. A particular distribution of spatially non-uniform growth is proposed which is considered representative of a vascular tumor. The stress distribution associated with this growth pattern predicts the onset of vascular collapse, producing the well-defined regions observed in vascular collapse experiments: a peripheral layer with open blood vessels adjacent to a region of vascular collapse, enclosing an inner region where the vessels are open. The model also highlights the roles of various tissue properties in inducing vascular collapse. Moreover, the tumor growth rates predicted by this model reflect experimental observations, with exponential growth taking place immediately following vascularization, followed by a period of exponential retardation.

Pancreatic ductal adenocarcinoma (PDA) responds poorly to chemotherapy. In this issue of Cancer Cell, Provenzano et al. identify hyaluronan as a pivotal determinant of elevated interstitial fluid pressures (IFP) and vascular collapse in PDA. PEGPH20 treatment ablates stromal hyaluronan, normalizes IFP, and increases accessibility of tumor cells to anticancer drugs.

In the study by Joo et al (1), perfusion-sensitive parameters derived from diffusion-weighted (DW) magnetic resonance (MR) imaging using intravoxel incoherent motion (IVIM) analysis were significantly decreased 4 hours after administration of a vascular disrupting agent (VDA) (CKD-516), in keeping with drug-induced vascular collapse. A larger decrease in the perfusion-sensitive IVIM parameters was correlated with smaller tumor size increase 7 days after treatment.

Intraosseous (IO) infusion is mainly used as an alternative for the vascular access when obtaining an intravenous (IV) access is difficult. Since recently, IO access is also useful as the initial access in cardiac arrest. Obtaining emergent IV access can be difficult, unacceptably time consuming and may be almost impossible in case of vascular collapse. Vascular collapse may occur in critically ill children in emergency situations such as hypovolemic shock or cardiac arrest. Therefore IO infusion is an important technique in the guidelines of pediatric cardiopulmonary resuscitation (CPR).

The remarkable accuracy of Walter B. Cannon’s 1942 article “ ‘Voodoo’ Death,” excerpted in this issue of the Journal,1 proposing a scientific basis for “voodoo” death is at once surprising and not surprising. Voodoo death, as defined by Cannon, is sudden, unexplained death resulthing from a voodoo curse. At first glance, it is surprising that scientific discoveries over the last 60 years have largely filled out the details of—but not overturned—most of Cannon’s proposed explanation of the physiological underpinnings of this phenomenon. On the other hand, it is not surprising when one considers the fact that Cannon’s research formed the basis for much of our modern understanding of the physiological response systems involved in linking emotions, such as fear, with illness. If submitted to a scientific journal today, this paper would not make it beyond the review process, as it would be described (probably with some disdain) as simply “anecdotal” and hypothetical. However, fortunately for our generation, our predecessors were apparently not averse to recording oral reports of inexplicable phenomena in detail—even down to the names of the individuals who experienced or perpetrated these events. Thus, Cannon starts his article with several anecdotal case reports, all of which share several important features that lead him to propose, first, that there may indeed be a physiological basis for the phenomenon of voodoo death and, second, what that physiological basis might be. The dramatic suddenness of the illness following the threat, coupled with a lack of any apparent injury, exposure to toxins, or infection suggested to Cannon that merely the fear of death could, through physiological response mechanisms initiated by fear, precipitate death itself. Cannon focused on the “sympathetic” and “sympathicoadrenal” divisions of the nervous system—terms still in use today (although “sympatho-adrenal” is now the more common term). He outlines all the aspects of bodily function over which this arm of the nervous system exerts control—blood vessel contraction, dilation of bronchioles, adrenaline release, release of sugar from the liver—all effects that together prepare the animal to attack or run—to “fight or flee.” Cannon thus elegantly lays out both the physiology and the evolutionary rationale for the “fight or flight response,” a term still in use today that he coined to describe this neurophysiological–behavioral response pattern. We could not have provided a better rationale for this aspect of the phenomenon today. This piece has stood the test of time. In the 60 years since Cannon first published his work, we have simply gained a clearer understanding of the brain regions that become activated when a fearful stimulus is experienced and a better road map of the pathways linking those brain centers involved in receiving sensory signals (in Cannon’s example, seeing a bone pointed at one) to the part of the brain that processes the emotional component of fear—the amygdala. In today’s terms, we would call this the “vision-to-fear pathway” or “auditory-to-fear pathway,” depending on the sense through which the threat is initially received. We have a deeper understanding of the neurotransmitters and neuropeptides involved in initiating these responses and perpetuating them through learning and memory. We know how such chemical signals are translated into electrical impulses and how quickly or slowly they are conveyed along nerve fibers. And we now know that such nerve chemicals and proteins are made by genes within the nucleus of nerve cells, that are switched on and off by all sorts of chemical and physical signals. We know that when we learn to fear something there are permanent changes in the shape and wiring of nerve cells that make it more likely that the next time we experience the fearful stimulus, those same pathways will be switched on all the more rapidly. Strikingly absent, however, from Cannon’s explanation is the hormonal stress response—the cascade of hormones released from the brain, pituitary gland, and adrenal gland within minutes of exposure to any sort of stressor. This is because in 1942, when the article was written, many of these hormones were yet to be discovered. Furthermore, the term “stress,” popularized by Cannon’s admirer Hans Selye and others in the postwar period, was not yet in general use. The structure of cortisol, the hormone released from the cortex of the adrenal glands during stress, was identified in 1936 by Edward Kendall and Tadeus Reichstein,2,3 who received the Nobel Prize for their discoveries in 1950 together with Philip Hench. However, the full cascade of hormones involved in the hormonal stress response was not fully elucidated until the identity of the brain’s hypothalamic stress hormone, corticotropin releasing hormone or CRH, was discovered by Wylie Vale in 1981.4 Thus, Cannon could not have included in his scenario of the possible causes of voodoo death the role of hypothalamic CRH released after signals from the amygdala, the brain’s fear center, reached the hypothalamus. Nor could he include how the cross-talk between the brain stem adrenaline centers involved in initiation of the sympathetic response could coordinate with hormones released from the brain’s hypothalamic stress center5 to cause a massive release of both adrenaline-like nerve chemicals and stress hormones. Together these might well cause illness,6–9 including loss of appetite, weakness, cardiac arrhythmias, and even vascular collapse that could result in death. Thus, Cannon’s rather simplistic explanation of how shock could ensue simply by removal of blood volume through sympathetic clamping of peripheral arterioles is in part correct, but he could not know of the complexity of hormones and nerve chemicals that, when all released together, might be more likely to produce the cardiac arrhythmias and vascular collapse than he predicted. Finally, he did not have the tools to go beyond hypothesis into the experimental stage in humans—to measure the responses he predicted and to prove through such measures which parts of his hypotheses were correct. He could not, as we can today, use neuroimaging technologies, electroencephalograms, and even single neuron recordings to measure nerve cell activation in different stress- and fear-related brain regions. He could not use telemetry devices and complex computer-generated mathematical analyses to noninvasively measure changes in heart rate variability, blood pressure, and cardiac blood flow in humans while they are going about their daily routines. Nor could he ask his subjects to respond to questions, programmed in their palm-pilots and synchronized with their heart rate monitors, about their moment-tomoment emotional states, to indicate within milliseconds whether a given threat caused a particular arrhythmia. He could not imagine that one could measure minute amounts of stress hormones and nerve chemicals released into the saliva during fear, simply by asking the subject to chew on a lemon-soaked cotton swab and spit into a cup. And he could not imagine how such hormones and nerve chemicals could possibly affect cells of the immune system to cause chronic wasting or disease. Cannon could not imagine how one could accomplish all this because the tools of neuroscience, molecular biology, computational mathematics, bioengineering, neuroimaging, endocrinology, and cellular immunology had not yet been invented or discovered. But, on the basis of observation, logic, and deduction, he did imagine that there could be a biological basis to the seemingly magical phenomenon of voodoo death. And, what’s more, he had the courage to predict and record in writing that there should be, some day, a way to get the answers. In this, Cannon was perhaps among the first physiologists to apply his scientific background to attempt to explain otherwise inexplicable illnesses and phenomena that seemed to link emotions and disease. This approach, combining open-mindedness and scientific rigor, is the essence of modern complementary and alternative medicine research.

Udgivelsesdato: 2010-null The vascular supply of tumours and the tumour microenvironment both play an important role when tumours are treated with hyperthermia. Blood flow is one of the major vehicles by which heat is dissipated thus the vascular supply will influence the ability to heat the tumour. It also influences the type of microenvironment that exists within tumours, and it is now well-established that cells existing in areas of oxygen deficiency, nutrient deprivation and acidic conditions are more sensitive to the effect of hyperthermia. The vascular supply and microenvironment are also affected by hyperthermia. In general, mild heat temperatures transiently improve blood flow and oxygenation, while higher hyperthermia temperatures cause vascular collapse and so increase the adverse microenvironmental conditions. Being able to image these vascular and microenvironmental parameters both before and after heating will help in our ability to predict and assess response. Here we review the various techniques that can be applied to supply this information, especially using non-invasive imaging approaches.

Vascular disrupting agents (VDAs) are distinguished from anti-angiogenic agents by their ability to cause a catastrophic vascular collapse in tumour tissue within minutes to hours of drug administration, leading to extensive tumour cell necrosis. Notwithstanding these effects, anti-angiogenic effects of VDAs can also be seen when they are administered in chronic dosing schedules. The largest group of VDAs is the tubulin-binding, microtubule-depolymerising combretastatins, with CA-4-P the lead compound. DMXAA is the other notable VDA currently in clinical trials. CA-4-P and DMXAA have different primary targets but are likely to have some mechanisms in common, notably involving the actin cytoskeleton. Extended vascular shut-down, which is necessary for tumour cell kill, requires a complex series of events which is only partially understood at present. Understanding and circumventing development of treatment resistance is also an important challenge. Nevertheless, phase I and II clinical trials have produced encouraging results for current VDAs and this approach holds the promise of providing a valuable new treatment choice to complement existing cancer therapy.

Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. Platelet-activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in various shock syndromes, including anaphylaxis. Excessive production of the vasodilator NO causes inflammatory hypotension and shock, and it is generally accepted that transcriptionally regulated inducible iNOS is responsible for this. Nevertheless, the contribution of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock depended entirely on NO, produced not by inducible iNOS, but by constitutive eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is generally regarded as the principal vasorelaxing mediator of NO. Nevertheless, although methylene blue partially prevented PAF shock, neither 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGCalpha1 deficiency did. Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS, PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the unsubstantiated paradigm that only excessive iNOS-derived NO underlies cardiovascular collapse in shock, our data strongly support the unexpected concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock and define eNOS and/or PI3K or Akt as new potential targets for treating anaphylaxis.

Intraosseous administration of resuscitation medications and fluids in preterm and term neonates is an alternative when intravascular access is not possible with intravenous catheters or needles. Intraosseous access is rarely needed in neonates because of the availability of clinicians with expert technical skills for placement of intravenous catheters in neonatal ICUs, the presence of the umbilical vein during the first days after birth when most resuscitations occur, and the predominance of resuscitations being responsive to positive-pressure ventilation alone. Intraosseous access is most likely to be needed in out-of-hospital settings and in hospitalized infants without intravenous access who have vascular collapse secondary to shock or when clinicians responsible for vascular access during resuscitations are more skilled in intraosseous access than intravenous access.

A mathematical model of residual stress evolution in a growing vascular tumour is presented, in an attempt to elucidate the poorly understood phenomenon of vascular collapse. Whereas earlier studies in this area have neglected the effects of mechanical interactions between the tumour and the surrounding host tissue, the significance of these interactions for the long-term development of a tumour is now considered. The model predicts tumour stress distributions which reflect the distinctive patterns of vascular collapse reported in experimental studies. Moreover, while neglecting mechanical host/tumour interactions results in the eventual complete regression of the tumour to its avascular dormant size in the event of vascular collapse, this new model points to the possibility of oscillations in the tumour's size in the long term.

— We have used the technique of dynamic capillaroscopy to study the time-course of photo-dynamic vascular occlusion in mice injected intraperitoneally with either of two photosensitizers; hematoporphyrin esters (HPE) or meso-tetrahydroxyphenyl chlorin (mTHPC). The peak of vascular occlusion induced by HPE coincided in time with peak serum levels of this photosensitizer (about 3 h after injection). However, there was also a second peak of occlusive activity at about 12 h after injection, at which time serum HPE was falling monotonically. In the case of mTHPC, no peak of occlusive activity was seen at 3 h after injection, even though the serum levels of this photosensitizer, like those of HPE, were highest around this time. Instead, a steady rise in photosensitizing activity was observed, peaking at 11 h. This decoupling between serum drug levels and vascular photosensitization—partial for HPE and complete for mTHPC—suggests that direct photosensitization of endothelial cells is unlikely wholly to explain the vascular collapse. Instead, there must be either another compartment that accumulates photosensitizer more slowly and in which photodynamic activity has an indirect effect on the blood capillaries or a slow metabolic transformation of mTHPC into a more active sensitizer.

The distribution and transport of fluid, ions, and other solutes (plasma proteins and glucose) are described in a mathematical model of unresuscitated hemorrhage. The model is based on balances of each material in both the circulation and its red blood cells, as well as in a whole-body tissue compartment along with its cells. Exchange between these four compartments occurs by a number of different mechanisms. The hemorrhage model has as its basis a validated model, due to Gyenge et al., of fluid and solute exchange in the whole body of a standard human. Hypothetical but physiologically based features such as glucose and small ion releases along with cell membrane changes are incorporated into the hemorrhage model to describe the system behavior, particularly during larger hemorrhages. Moderate (10%-30% blood volume loss) and large (> 30% blood loss) hemorrhage dynamics are simulated and compared with available data. The model predictions compare well with the available information for both types of hemorrhages and provide a reasonable description of the progression of a large hemorrhage from the compensatory phase through vascular collapse.

The authors have developed a soft tissue model that predicts the mechanical response of a solid tumor to its host environment. The effects of leaky vessels, lack of functional lymphatics, and tissue growth due to cell division were incorporated as distributed parameters into a poroelastic continuum model. The resulting simulations chronicled the evolution of high fluid pressure and solid stress regions within the tumor interstitium as a function of both expansion and age. In this study, the authors focused on two different applications of the model. By determining regions of sufficiently high stress, the poroelastic solution was used to predict the onset of vascular instability as caused by cell proliferation. The second application of the mechanical model of cancer was towards understanding biological transport in the tumor system. Pharmacokinetic models were developed that incorporate high interstitial pore pressure and the fluid flux barrier as determined from the poroelastic pore pressure solution. Spatial and temporal distributions of macromolecular therapeutic agents were determined within the tumor-host system, and the resulting simulations revealed an age dependent response.

La hidatidosis es una enfermedad endémica en el área mediterránea, pero su presentación como shock anafiláctico sólo acontece en un escaso porcentaje, oscilando entre un 1 y un 7,5%. Esta manifestación se produce al romperse el quiste hidatídico, liberando al exterior su contenido. El diagnóstico etiológico es fácil cuando el shock se presenta durante la manipulación quirúrgica del quiste hidatídico, pero la dificultad surge cuando se produce por la rotura espontánea del mismo. Se debe sospechar en pacientes sanos que vivan en zonas endémicas y que presenten súbitamente un cuadro de colapso vascular. No suele haber antecedentes de quistes hidatídicos en estos pacientes, aunque la historia clínica suele poner de manifiesto la existencia de antecedentes compatibles con procesos alérgicos no filiados.

Major errors were found in 44%, moderate errors in 28%, and minor errors in 12% in the adult laboratories. In the pediatric echocardiography laboratory, there were major errors in 0%, moderate errors in 4%, and minor errors in 4% of patients. When duplicate echocardiographic studies were available, the rates of major, moderate, and minor errors in adult laboratories were 12%, 29%, and 12%. There were no errors in the studies performed by pediatric echocardiographers. Of the errors made in the adult echocardiography laboratories, 71% were interpretive, 17% were technical, and 11% were both. Error incidences were not related to patient age, study year, use of color Doppler, or complexity of diagnoses. In total, moderate or major errors were noted in 35 of 65 patients. In 29 of the 35 patients, subsequent echocardiograms performed in a pediatric laboratory resulted in altered clinical management, including 12 surgeries and 2 averted cardiac operations. In 3 of the 29 patients, delayed diagnoses were associated with fixed pulmonary vascular disease, hypoxemic spells, and vascular collapse with severe metabolic acidosis. These findings support the importance of thorough training in pediatric echocardiography in a suitable high-volume laboratory.

Our results showed more rapid falls in pulse rate and blood pressure in rats euthanized in a chamber precharged with carbon dioxide (CO2), when compared with rats euthanized more slowly, but death still took over 5 min in the former group. There was no behavioural evidence of pain or distress in either group during euthanasia. Initial ataxia and dyspnoea was punctuated by a lag before death, thus separating euthanasia into three clearly defined phases. All visual signs of death preceded complete vascular collapse by about 1 min in both groups, so we recommend that gas flow be maintained for at least 1 min after apparent death.

Tumor growth is strongly coupled with both residual stress generated during the growth process and also biochemical factors. Several models have already been proposed to capture tumor growth considering either diffusion of nutrients concentration or residual stresses inside a tumor. In this work, a new method was proposed to model the generated residual stress in a growing solid using the continuum framework. This method was coupled with energy metabolism to predict the behavior of a soft tissue tumor. Moreover, it was shown that the main reason of vascular collapse in the middle of a tumor or vascular reopening in the tumor core can be the residual stress, generated during the growth.

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin that is rapidly progressive and is accompanied by vascular collapse and disseminated intravascular coagulation. It usually occurs in children, but this syndrome has also been noted in adults. The three forms of this disease are classified by the triggering mechanisms. We describe three classical cases of purpura fulminans of the three classical prototypes treated at our center and their varied clinical outcomes. We also describe a case of acute infectious purpura fulminans secondary to systemic leptospirosis which to our best knowledge is the first reported case in world literature. The various treatment options for purpura fulminans have also been reviewed.

Anaphylaxis is a potentially life-threatening systemic allergic reaction, often with an explosive onset; the symptoms range from mild flushing to upper respiratory obstruction, with or without vascular collapse. Foods are common offending allergens and remain the leading cause of outpatient anaphylaxis in most surveys. Yacon (Smallanthus sonchifolius) is a plant native to the Andes region, where its root is cultivated and consumed mainly as food. Unlike most edible roots, yacon contains large amounts of ructooligosaccharides. Traditionally, yacon tubers have been used as a source of natural sweetener and syrup for people suffering from various disorders. We report the case of a 55-year-old woman who developed syncope and generalized urticaria after ingesting yacon roots. The patient had positive skin prick and intradermal tests to yacon extract. An open food challenge test was performed to confirm food anaphylaxis and was positive 10 minutes after the consumption of yacon roots. To our knowledge, this is the first reported case of anaphylaxis after the ingestion of yacon roots.