Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea.

Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.

Intermittent Hypoxia and Diet-Induced Obesity on the Intestinal Wall Morphology in a Murine Model of Sleep Apnea.

This work analyzes the impact of two conditions, intermittent hypoxia exposure and high-fat diet in rats as models of sleep apnea. We studied the autonomic activity and histological structure of the rat jejunum and whether the overlapping of both conditions, as often observed in patients, induces more deleterious effects on the intestinal barrier. We found alterations in jejunum wall histology, predominantly in HF rats, based on increased crypt depth and submucosal thickness, as well as decreased muscularis propria thickness. These alterations were maintained with the IH and HF overlap. An increase in the number and size of goblet cells in the villi and crypts and the infiltration of eosinophils and lymphocytes in the lamina propria suggest an inflammatory status, confirmed by the increase in plasma CRP levels in all experimental groups. Regarding the CAs analysis, IH, alone or combined with HF, causes a preferential accumulation of NE in the catecholaminergic nerve fibers of the jejunum. In contrast, serotonin increases in all three experimental conditions, with the highest level in the HF group. It remains to be elucidated whether the alterations found in the present work could affect the permeability of the intestinal barrier, promoting sleep apnea-induced morbidities.

Actinomicosis que simula un tumor esofágico / No disponible

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Esophageal actinomycosis mimicking a carcinoma.

A 75-year-old male was referred due to dysphagia and iron-deficiency anemia. An upper endoscopy was performed which revealed a friable mass at 30 to 37 cm from the incisors, consistent with esophageal malignancy. However, the pathology only demonstrated granulation inflammatory tissue. An endoscopic ultrasound exam showed a 2-3 cm esophageal wall thickening with a 1.5 cm lymph node, which was staged as a T2-3 N1 esophageal tumor. A CT-scan also identified a 7.5 cm esophageal malignancy surrounded by several large pathological lymph nodes.

Adenoma suprarrenal gigante con degeneración quística hemorrágica / Giant adrenal adenoma with hemorrhagic cystic degeneration

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Adrenal Medulla Chemo Sensitivity Does Not Compensate the Lack of Hypoxia Driven Carotid Body Chemo Reflex in Guinea Pigs.

Guinea pigs (GP), originally from the Andes, have absence of hypoxia-driven carotid body (CB) reflex. Neonatal mammals have an immature CB chemo reflex and respond to hypoxia with metabolic changes arising from direct effects of hypoxia on adrenal medulla (AM). Our working hypothesis is that adult GP would mimic neonatal mammals. Plasma epinephrine (E) has an AM origin, while norepinephrine (NE) is mainly originated in sympathetic endings, implying that specific GP changes in plasma E/NE ratio, and in blood glucose and lactate levels during hypoxia would be observed. Experiments were performed on young adult GP and rats. Hypoxic ventilation (10% O2) increased E and NE plasma levels similarly in both species but PaO2 was lower in GP than in rats. Plasma E/NE ratio in GP was higher (≈1.0) than in rats (≈0.5). The hypoxia-evoked increases in blood glucose and lactate were smaller in GP than in the rat. The AM of both species contain comparable E content, but NE was four times lower in GP than in rats. GP superior cervical ganglion also had lower NE content than rats and an unusual high level of dopamine, a negative modulator of sympathetic transmission. Isolated AM from GP released half of E and one tenth of NE than the rat AM, and hypoxia did not alter the time course of CA outflow. These data indicate the absence of direct effects of hypoxia on AM in the GP, and a lower noradrenergic tone in this species. Pathways for hypoxic sympatho-adrenal system activation in GP are discussed.

Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

Acute esophageal necrosis resolved in 72 hours.

We report a case of acute esophageal necrosis whose initial symptom was sudden dysphagia and was completely resolved in 72 hours.

Necrosis aguda de esófago resuelta en 72 horas / Acute esophageal necrosis resolved in 72 hours

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Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study.

Stage I-II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I-II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient's total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/µL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62-0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I-II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.

Endoscopic diagnosis of asymptomatic perforation of colonic diverticulum.

Colonic perforation as complication of acute diverticulitis is a relatively frequent pathology and generally very symptomatic. Nevertheless, when it occurs in the mesenteric border the course can be indolent.

Fernando de Castro and the discovery of the arterial chemoreceptors.

When de Castro entered the carotid body (CB) field, the organ was considered to be a small autonomic ganglion, a gland, a glomus or glomerulus, or a paraganglion. In his 1928 paper, de Castro concluded: "In sum, the Glomus caroticum is innervated by centripetal fibers, whose trophic centers are located in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent] or secretomotor fibers as is the case for glands; these are precisely the facts which lead to suppose that the Glomus caroticum is a sensory organ." A few pages down, de Castro wrote: "The Glomus represents an organ with multiple receptors furnished with specialized receptor cells like those of other sensory organs [taste buds?]…As a plausible hypothesis we propose that the Glomus caroticum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that, possibly by a reflex mechanism would have an effect on the functional activity of other organs… Therefore, the sensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cells of the organ, which, as their structure suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers." In our article we will recreate the experiments that allowed Fernando de Castro to reach this first conclusion. Also, we will scrutinize the natural endowments and the scientific knowledge that drove de Castro to make the triple hypotheses: the CB as chemoreceptor (variations in blood composition), as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemic reflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we will complete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functioning of this arterial chemoreceptor.

Effects of cigarette smoke and chronic hypoxia on ventilation in guinea pigs. Clinical significance.

Ventilatory effects of chronic cigarette smoke (CS) alone or associated to chronic hypoxia (CH), as frequently occurs in chronic obstructive pulmonary disease (COPD), remain unknown. We have addressed this problem using whole-body plethysmography in guinea-pigs, common models to study harmful effects of CS on the respiratory system. Breathing frequencies (Bf) in control (2-5 months old) guinea pigs is 90-100 breaths/min, their tidal volume (TV) increased with age but lagged behind body weight gain and, as consequence, their minute volume (MV)/Kg decreased with age. MV did not change by acutely breathing 10% O(2) but doubled while breathing 5% CO(2) in air. Exposure to chronic sustained hypoxia (15 days, 12% O(2), CH) did not elicit ventilatory acclimatization nor adaptation. These findings confirm the unresponsiveness of the guinea pig CB to hypoxia. Exposure to CS (3 months) increased Bf and MV but association with CH blunted CS effects. We conclude that CS and CH association accelerates CS-induced respiratory system damage leading to a hypoventilation that can worsen the ongoing COPD process.

Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance.

Previously we have reported that association of cigarette smoke (CS) and chronic hypoxia (CH) interact positively to physiopathologically remodel pulmonary circulation. In present study we have exposed guinea pigs to CS smoke (four cigarettes/day; 3 months; CS) and to chronic hypoxia (12% O(2), 15 days; CH) alone or in combination (CSCH animals) and evaluated airways remodeling and resistance assessed as Penh (enhance pause). We measured Penh while animals breathe air, 10% O(2) and 5% CO(2) and found that CS and CH animals have higher Penh than controls; Penh was even larger in CSCH animals. A rough parallelism between Penh and thickness of bronchiolar wall and muscular layer and Goblet cell number was noticed. We conclude that CS and CH association accelerates CS-induced respiratory system damage, evidenced by augmented airway resistance, bronchial wall thickness and muscularization and Goblet cell number. Our findings would suggest that appearance of hypoxia would aggravate any preexisting pulmonary pathology by increasing airways resistance and reactivity.

Gastric hyperplastic polyps: a heterogeneous clinicopathologic group including a distinct subset best categorized as mucosal prolapse polyp.

BACKGROUND: Gastric hyperplastic polyps are the second most common subtype of gastric polyps. There has been an ongoing debate about their precise diagnostic criteria and etiological associations. MATERIALS AND METHODS: A total of 208 gastric polyps that were originally diagnosed as hyperplastic polyps in our department during an 8-year period were reviewed using recently emphasized diagnostic criteria, and their clinicopathologic associations were explored. RESULTS: Only 41 cases were confirmed as hyperplastic polyps, whereas 103 cases (49%) were reclassified as polypoid foveolar hyperplasia, and 64 cases (31%) were diagnosed as gastric mucosal prolapse polyps. Gastric mucosal prolapse polyps were distinguished by basal glandular elements, hypertrophic muscle fibers ascending perpendicularly from the muscularis mucosae, and by thick-walled blood vessels. This hitherto undescribed polyp is more commonly sessile than hyperplastic polyps (P=0.0452) and is found more often in the antropyloric region (P: 0.0053). Only 20.6% of hyperplastic polyps were associated with Helicobacter pylori infection. CONCLUSIONS: Our findings highlight that gastric polypoid lesions that have morphologic similarities may be related to various mechanisms, including inflammatory and prolapse processes. The predominantly antral location of gastric mucosal prolapse polyps, a zone of pronounced peristalsis, suggests that mucosal prolapse plays a role in the development of these common polyps. Evaluation of the prevalence and clinical associations of these distinctive polyps awaits further studies.

Intravascular ultrasound and histology findings in very late bare-metal stent thrombosis.

Very late thrombosis in an implanted bare-metal stent is a very uncommon event outside the context of brachytherapy and few data about its pathophysiology are available. We performed an intravascular ultrasound study during primary angioplasty in five patients with very late bare-metal stent thrombosis and carried out a histological analysis of the material removed by manual thrombectomy. The mean time from the index procedure was 7 ± 4 years. Intravascular ultrasound findings were: calcified atherosclerosis with in-stent plaque rupture, complex plaque in the distal segment of the stent, in-stent neointimal proliferation associated with underexpansion, and severe in-stent proliferation. Histological findings were consistent with the intravascular ultrasound images: recent thrombus with areas of old thrombosis in all cases and remnant atheromatous plaque and endothelium. Consequently, in-stent or distal stent atherosclerosis progression and progressive neointimal proliferation were the likely pathophysiological mechanisms.

Hallazgos de ecografía intravascular e histológicos de trombosis muy tardías de stents convencionales / Intravascular ultrasound and histology findings in very late bare-metal stent thrombosis

La trombosis muy tardía tras el implante de un stent convencional es un evento muy infrecuente fuera del contexto de la braquiterapia y apenas existen datos sobre su fisiopatología. Estudiamos a 5 pacientes con trombosis muy tardía tras stent convencional a quienes se realizó ecografía intravascular durante el intervencionismo primario y análisis histológico del material extraído tras trombectomía manual. La media de tiempo desde el implante fue 7 ± 4 años. Los hallazgos ecográficos fueron: aterosclerosis calcificada con placa rota intra-stent, placa compleja en el borde distal del stent, proliferación neointimal intra-stent en relación con infraexpansión y proliferación severa intra-stent. La histología fue concordante con la imagen intravascular: trombo reciente con zonas de trombosis antigua en todos los casos y restos de placa de ateroma y endotelio. Por lo tanto, la progresión de la aterosclerosis intra-stent o en bordes y la progresión de la proliferación neointimal fueron los factores fisiopatológicos plausibles (AU)

Very late thrombosis in an implanted bare-metal stent is a very uncommon event outside the context of brachytherapy and few data about its pathophysiology are available. We performed an intravascular ultrasound study during primary angioplasty in five patients with very late bare-metal stent thrombosis and carried out a histological analysis of the material removed by manual thrombectomy. The mean time from the index procedure was 7±4 years. Intravascular ultrasound findings were: calcified atherosclerosis with in-stent plaque rupture, complex plaque in the distal segment of the stent, in-stent neointimal proliferation associated with underexpansion, and severe in-stent proliferation. Histological findings were consistent with the intravascular ultrasound images: recent thrombus with areas of old thrombosis in all cases and remnant atheromatous plaque and endothelium. Consequently, in-stent or distal stent atherosclerosis progression and progressive neointimal proliferation were the likely pathophysiological mechanisms (AU)