A rare cause of chronic mesenteric ischemia from fibromuscular dysplasia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chronic mesenteric ischemia is a condition that is classically associated with significant atherosclerosis of the abdominal arteries, causing postprandial abdominal pain out of proportion to physical examination. The abdominal pain is exacerbated after meals due to the shunting of blood away from the intestines to the stomach, causing relative ischemia. More than 95% of chronic mesenteric ischemia cases are due to atherosclerosis. We report the first known case of chronic mesenteric ischemia from fibromuscular dysplasia. To the best of our knowledge, this is also the first known case in the literature where postprandial abdominal pain was the presenting symptom of fibromuscular dysplasia.</p> <p>Case presentation</p> <p>A 44-year-old Caucasian woman with a history of hypertension and preeclampsia, who had taken oral contraceptive pills for 15 years, presented with an intractable, colicky abdominal pain of two weeks duration. This abdominal pain worsened with oral intake. It was also associated with diarrhea and vomiting. Physical examination revealed stage III hypertension out of proportion to her risk factors and diffuse abdominal pain without peritoneal signs. An abdominal computed tomography scan, completed in the emergency room, revealed nonspecific colitis. Laboratory work revealed leukocytosis with a left shift, an erythrocyte sedimentation rate of 79 and a C-reactive protein level of 100. She was started on intravenous flagyl and intravenous ciprofloxacin. However, all microbial cultures were negative including three cultures for clostridium difficile. Urine analysis revealed nephritic range proteinuria. The laboratory profile was within normal limits for perinuclear-anti-neutrophil cytoplasmic antibody, cytoplasmic-anti-neutrophil cytoplasmic antibody, anti-saccharomyces cerevisiae antibody, antinuclear antibody test, celiac profile, lactate, carbohydrate antigen-125 and thyroid stimulating hormone. A colonoscopy was completed, which revealed diffuse colonic lymphoid reactive hyperplasia. A small bowel series was negative for any inflammation. An indium scan, pan-computed tomography scan and transvaginal ultrasound were also negative. Magnetic resonance angiography of her abdomen revealed proximal superior mesenteric artery stenosis, which was confirmed by computed tomography angiogram findings of severe proximal and distal superior mesenteric artery stenosis, consistent with the appearance of fibromuscular dysplasia on angiography in the absence of vasculitis or atherosclerotic disease. The patient's superior mesenteric artery stenosis was subsequently angioplastied suboptimally and had to be stented with an Angioplus stent. One month after she was admitted, her abdominal pain and tolerance to oral feeds improved tremendously.</p> <p>Conclusion</p> <p>Fibromuscular dysplasia most commonly presents with renal artery stenosis, which rarely causes abdominal pain. This case illustrates how fibromuscular dysplasia can present as a rare cause of chronic mesenteric ischemia, similar to chronic mesenteric ischemia from atherosclerosis.</p

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

A Meta-Analysis of Seaweed Impacts on Seagrasses: Generalities and Knowledge Gaps

Seagrasses are important habitat-formers and ecosystem engineers that are under threat from bloom-forming seaweeds. These seaweeds have been suggested to outcompete the seagrasses, particularly when facilitated by eutrophication, causing regime shifts where green meadows and clear waters are replaced with unstable sediments, turbid waters, hypoxia, and poor habitat conditions for fishes and invertebrates. Understanding the situations under which seaweeds impact seagrasses on local patch scales can help proactive management and prevent losses at greater scales. Here, we provide a quantitative review of available published manipulative experiments (all conducted at the patch-scale), to test which attributes of seaweeds and seagrasses (e.g., their abundances, sizes, morphology, taxonomy, attachment type, or origin) influence impacts. Weighted and unweighted meta-analyses (Hedges d metric) of 59 experiments showed generally high variability in attribute-impact relationships. Our main significant findings were that (a) abundant seaweeds had stronger negative impacts on seagrasses than sparse seaweeds, (b) unattached and epiphytic seaweeds had stronger impacts than ‘rooted’ seaweeds, and (c) small seagrass species were more susceptible than larger species. Findings (a) and (c) were rather intuitive. It was more surprising that ‘rooted’ seaweeds had comparatively small impacts, particularly given that this category included the infamous invasive Caulerpa species. This result may reflect that seaweed biomass and/or shading and metabolic by-products like anoxia and sulphides could be lower for rooted seaweeds. In conclusion, our results represent simple and robust first-order generalities about seaweed impacts on seagrasses. This review also documented a limited number of primary studies. We therefore identified major knowledge gaps that need to be addressed before general predictive models on seaweed-seagrass interactions can be build, in order to effectively protect seagrass habitats from detrimental competition from seaweeds

Definitive hypofractionated radiotherapy for early glottic carcinoma: experience of 55Gy in 20 fractions

Introduction: A wide variety of fractionation schedules have been employed for the treatment of early glottic cancer. The aim is to report our 10-year experience of using hypofractionated radiotherapy with 55Gy in 20 fractions at 2.75Gy per fraction. Methods: Patients treated between 2004 and 2013 with definitive radiotherapy to a dose of 55Gy in 20 fractions over 4 weeks for T1/2 N0 squamous cell carcinoma of the glottis were retrospectively identified. Patients with prior therapeutic minor surgery (eg. laser stripping, cordotomy) were included. The probabilities of local control, ultimate local control (including salvage surgery), regional control, cause specific survival (CSS) and overall survival (OS) were calculated. Results: One hundred thirty-two patients were identified. Median age was 65 years (range 33–89). Median follow up was 72 months (range 7–124). 50 (38 %), 18 (14 %) and 64 (48 %) of patients had T1a, T1b and T2 disease respectively. Five year local control and ultimate local control rates were: overall - 85.6 % and 97.3 % respectively, T1a - 91.8 % and 100 %, T1b - 81.6 and 93.8 %, and T2 - 80.9 % and 95.8 %. Five year regional control, CSS and OS rates were 95.4 %, 95.7 % and 78.8 % respectively. There were no significant associations of covariates (e.g. T-stage, extent of laryngeal extension, histological grade) with local control on univariate analysis. Only increasing age and transglottic extension in T2 disease were significantly associated with overall survival (both p <0.01). Second primary cancers developed in 17 % of patients. 13 (9.8 %) of patients required enteral tube feeding support during radiotherapy; no patients required long term enteral nutrition. One patient required a tracheostomy due to a non-functioning larynx on long term follow up. Conclusions: Hypofractionated radiation therapy with a dose of 55Gy in 20 fractions for early stage glottic cancer provides high rates of local control with acceptable toxicity

Organ preservation surgery for laryngeal cancer

The principles of management of the laryngeal cancer have evolved over the recent past with emphasis on organ preservation. These developments have paralleled technological advancements as well as refinement in the surgical technique. The surgeons are able to maintain physiological functions of larynx namely speech, respiration and swallowing without compromising the loco-regional control of cancer in comparison to the more radical treatment modalities. A large number of organ preservation surgeries are available to the surgeon; however, careful assessment of the stage of the cancer and selection of the patient is paramount to a successful outcome. A comprehensive review of various organ preservation techniques in vogue for the management of laryngeal cancer is presented

Axonal Varicosity Density as an Index of Local Neuronal Interactions

Diffuse transmission is an important non-synaptic communication mode in the cerebral neocortex, in which neurotransmitters released from en passant varicosities interact with surrounding cells. In a previous study we have shown that the cholinergic axonal segments which were in the microproximity with dopaminergic fibers possessed a greater density of en passant varicosities compared to more distant segments, suggesting an activity-dependent level of en passant varicosities in the axonal zone of interaction. To further evaluate this plastic relationship, the density of cholinergic varicosities was quantified on fiber segments within the microproximity of activated or non-activated pyramidal cells of the prefrontal cortex (mPFC). Repetitive 14 days patterned visual stimulation paired with an electrical stimulation of the cholinergic fibers projecting to the mPFC from the HDB was performed to induce persistent axonal plastic changes. The c-Fos early gene immunoreactivity was used as a neuronal activity marker of layer V pyramidal cells, labelled with anti-glutamate transporter EAAC1. Cholinergic fibers were labeled with anti-ChAT (choline acetyltransferase) immunostaining. The density of ChAT+ varicosities on and the length of fiber segments within the 3 µm microproximity of c-Fos positive/negative pyramidal cells were evaluated on confocal images. More than 50% of the pyramidal cells in the mPFC were c-Fos immunoreactive. Density of ChAT+ varicosities was significantly increased within 3 µm vicinity of activated pyramidal cells (0.50±0.01 per µm of ChAT+ fiber length) compared to non-activated cells in this group (0.34±0.001; p≤0.05) or control rats (0.32±0.02; p≤0.05). Different types of stimulation (visual, HDB or visual/HDB) induced similar increase of the density of ChAT+ varicosities within microproximity of activated pyramidal cells. This study demonstrated at the subcellular level an activity-dependent enrichment of ChAT+ varicosities in the axonal zone of interaction with other neuronal elements

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear

Endothelium-derived endothelin-1

One year after the revelation by Dr. Furchgott in 1980 that the endothelium was obligatory for acetylcholine to relax isolated arteries, it was clearly shown that the endothelium could also promote contraction. In 1988, Dr. Yanagisawa’s group identified endothelin-1 (ET-1) as the first endothelium-derived contracting factor. The circulating levels of this short (21-amino acid) peptide were quickly determined in humans, and it was reported that, in most cardiovascular diseases, circulating levels of ET-1 were increased, and ET-1 was then tagged as “a bad guy.” The discovery of two receptor subtypes in 1990, ET(A) and ET(B), permitted optimization of the first dual ET-1 receptor antagonist in 1993 by Dr. Clozel’s team, who entered clinical development with bosentan, which was offered to patients with pulmonary arterial hypertension in 2001. The revelation of Dr. Furchgott opened a Pandora’s box with ET-1 as one of the actors. In this brief review, we will discuss the physiological and pathophysiological role of endothelium-derived ET-1 focusing on the regulation of the vascular tone, and as much as possible in humans. The coronary bed will be used as a running example in this review because it is the most susceptible to endothelial dysfunction, but references to the cerebral and renal circulation will also be made. Many of the cardiovascular complications associated with aging and cardiovascular risk factors are initially attributable, at least in part, to endothelial dysfunction, particularly dysregulation of the vascular function associated with an imbalance in the close interdependence of nitric oxide and ET-1