Down-regulation of angiopoietin-1 expression in menorrhagia

Angiogenesis is an essential component of endometrial repair and regeneration following menses. Perturbation of this process is associated with menorrhagia, a common gynecological disorder that results in excessive menstrual bleeding. Angiopoietin-1 (Ang-1) promotes vascular maturation via the Tie-2 receptor, while angiopoietin-2 (Ang-2) is its natural antagonist that destabilizes vessels and initiates neovascularization in the presence of vascular endothelial growth factor. To test the hypothesis that menorrhagia arises as a result of poor signal for vascular maturation, we have examined the expression of Ang-1, Ang-2, and Tie-2 in endometrium throughout the menstrual cycle from 30 normal women and 28 patients with menorrhagia. Ribonuclease protection assay and Western blot analysis showed Ang-2 expression was consistently higher than Ang-1 in normal endometrium throughout the cycle. However, with menorrhagia Ang-1 mRNA and protein were not detected or down-regulated, while Ang-2 was observed at similar levels in both normal and menorrhagic endometrium resulting in a greater than a 50% decrease in the ratio of Ang-1 to Ang-2 protein. In situ hybridization and immunohistochemical studies supported these findings and revealed cyclical changes in the expression of Ang-1 and Ang-2. These results suggest that the angiopoietin/Tie-2 system promotes vascular remodeling in endometrium and loss of normal Ang-1 expression may contribute to the excessive blood loss observed in menorrhagia.

Laparoscopic versus open total mesorectal excision for stage I-III mid and low rectal cancer: a retrospective 5 years analysis

Introduction. Total mesorectal excision (TME) is the cornerstone of a correct surgical therapy for extraperitoneal rectal cancer. Aim of the study is to evaluate our 5 years experience confronting retrospectively laparoscopic (lap) TME in respect to its laparotomic (open) counterpart. Patients and Methods. 30 patients were treated laparoscopically for stage I-III extraperitoneal rectal cancer and retrospectively compared to a homogeneous group, stratified for sex, age, comorbidities and stage of disease. Results. 30 days mortality was zero for both groups, while morbidity was 20% for the lap group and 36.6% for the open group. Mean lymph nodes harvested was 24 ± 12 for the lap group, 26 ± 14 for the open group (p > 0.05). Five years overall and disease free survival was respectively 82.2% and 81.4% in the lap group, 79.9% and 79.6% in the open group, without statistical significance (p>0.05). Discussion. Minimally invasive TME resulted a safe, effective and oncologically adequate procedure when retrospectively compared to its laparotomic counterpart, with 5 years overall survival and disease free survival reaching no statistical significance compared to the open approach, but with all the advantages of the laparoscopy such as less pain and blood loss, faster recovery, less morbidity and better cosmetics. Conclusions. Our study has retrospectively demonstrated that laparoscopic TME is feasible and oncologically effective, even if it remains a complex minimally invasive procedure, requiring adequate skill. More prospective, randomized studies are necessary to define such a procedure as the new gold standard in treatment of stage I-III extraperitoneal rectal cancer.

Non-acute Transient Reversible Adrenal Insufficiency in a Survivor of Critical Illness: A Lesser-known Cause of Primary Adrenal Insufficiency

Objectives: Primary adrenal insufficiency AI is regarded as a progressive disease needing lifelong replacement therapy, but this may not always be the case. Material and methods: A non-acute presentation of AI following a hypotensive episode caused by blood loss was investigated. Results: Adrenal function fully recovered without treatment. Conclusions: There should be a high index of suspicion and a low threshold for performing tests of adrenal function in survivors of critical illness and severe hypotensive episodes.

Trauma in critically ill children : transfusion and osmotherapy practices

Les accidents sont la cause la plus fréquente de décès chez l’enfant, la plupart du temps à cause d’un traumatisme cranio-cérébrale (TCC) sévère ou d’un choc hémorragique. Malgré cela, la prise en charge de ces patients est souvent basée sur la littérature adulte. Le mannitol et le salin hypertonique (3%) sont des traitements standards dans la gestion de l’hypertension intracrânienne, mais il existe très peu d’évidence sur leur utilité en pédiatrie. Nous avons entrepris une revue rétrospective des traumatismes crâniens sévères admis dans les sept dernières années, pour décrire l’utilisation de ces agents hyperosmolaires et leurs effets sur la pression intracrânienne. Nous avons établi que le salin hypertonique est plus fréquemment utilisé que le mannitol, qu’il ne semble pas y avoir de facteurs associés à l’utilisation de l’un ou l’autre, et que l’effet sur la pression intracrânienne est difficile à évaluer en raison de multiples co-interventions. Il faudra mettre en place un protocole de gestion du patient avec TCC sévère avant d’entreprendre des études prospectives. La transfusion sanguine est employée de façon courante dans la prise en charge du patient traumatisé. De nombreuses études soulignent les effets néfastes des transfusions sanguines suggérant des seuils transfusionnels plus restrictifs. Malgré cela, il n’y a pas de données sur les transfusions chez l’enfant atteint de traumatismes graves. Nous avons donc entrepris une analyse post-hoc d’une grosse étude prospective multicentrique sur les pratiques transfusionnelles des enfants traumatisés. Nous avons conclu que les enfants traumatisés sont transfusés de manière importante avant et après l’admission aux soins intensifs. Un jeune âge, un PELOD élevé et le recours à la ventilation mécanique sont des facteurs associés à recevoir une transfusion sanguine aux soins intensifs. Le facteur le plus prédicteur, demeure le fait de recevoir une transfusion avant l’admission aux soins, élément qui suggère probablement un saignement continu. Il demeure qu’une étude prospective spécifique des patients traumatisés doit être effectuée pour évaluer si une prise en charge basée sur un seuil transfusionnel restrictif serait sécuritaire dans cette population.

Trauma in critically ill children : transfusion and osmotherapy practices

Les accidents sont la cause la plus fréquente de décès chez l’enfant, la plupart du temps à cause d’un traumatisme cranio-cérébrale (TCC) sévère ou d’un choc hémorragique. Malgré cela, la prise en charge de ces patients est souvent basée sur la littérature adulte. Le mannitol et le salin hypertonique (3%) sont des traitements standards dans la gestion de l’hypertension intracrânienne, mais il existe très peu d’évidence sur leur utilité en pédiatrie. Nous avons entrepris une revue rétrospective des traumatismes crâniens sévères admis dans les sept dernières années, pour décrire l’utilisation de ces agents hyperosmolaires et leurs effets sur la pression intracrânienne. Nous avons établi que le salin hypertonique est plus fréquemment utilisé que le mannitol, qu’il ne semble pas y avoir de facteurs associés à l’utilisation de l’un ou l’autre, et que l’effet sur la pression intracrânienne est difficile à évaluer en raison de multiples co-interventions. Il faudra mettre en place un protocole de gestion du patient avec TCC sévère avant d’entreprendre des études prospectives. La transfusion sanguine est employée de façon courante dans la prise en charge du patient traumatisé. De nombreuses études soulignent les effets néfastes des transfusions sanguines suggérant des seuils transfusionnels plus restrictifs. Malgré cela, il n’y a pas de données sur les transfusions chez l’enfant atteint de traumatismes graves. Nous avons donc entrepris une analyse post-hoc d’une grosse étude prospective multicentrique sur les pratiques transfusionnelles des enfants traumatisés. Nous avons conclu que les enfants traumatisés sont transfusés de manière importante avant et après l’admission aux soins intensifs. Un jeune âge, un PELOD élevé et le recours à la ventilation mécanique sont des facteurs associés à recevoir une transfusion sanguine aux soins intensifs. Le facteur le plus prédicteur, demeure le fait de recevoir une transfusion avant l’admission aux soins, élément qui suggère probablement un saignement continu. Il demeure qu’une étude prospective spécifique des patients traumatisés doit être effectuée pour évaluer si une prise en charge basée sur un seuil transfusionnel restrictif serait sécuritaire dans cette population.

Factores asociados a transfusión sanguínea en el manejo quirúrgico del canal lumbar estrecho en la Fundación Santa Fe de Bogotá 2003 - 2013

Introduccion: El canal lumbar estrecho es un motivo de consulta frecuente en el servicio de columna de la Fundación Santa Fe de Bogotá. Derivado del tratamiento quirurgico se pueden generar múltiples complicaciones, entre las que se encuentra la transfusión sanguínea. Objetivo: Identificar los factores sociodemográficos, antecedentes personales y factores quirúrgicos asociados a transfusión sanguínea en cirugía canal lumbar estrecho en la Fundación Santa Fe de Bogotá 2003- 2013. Materiales y métodos: Se aplicó en diseño de estudio observacional analítico transversal. Se incluyeron 367 pacientes sometidos a cirugía de canal lumbar estrecho a quienes se les analizaron variables de antecedentes personales, características sociodemograficas y factores quirúrgicos. Resultados: La mediana de la edad fue de 57 años y la mayoría de pacientes fueron mujeres (55,6%). La mediana del Índice de Masa Corporal (IMC) fue de 24,9 clasificado como normal. Entre los antecedentes patológicos, la hipertensión arterial fue el más común (37,3%). La mayoría de pacientes (59,1%) presentaron clasificación ASA de II. El tipo de cirugía más prevalente fue el de descompresión (55,6%). En el 79,8% de los pacientes se intervinieron 2 niveles. Se realizó transfusión de glóbulos rojos en 26 pacientes correspondiente a 7,1% del total. En la mayoría de procedimientos quirúrgicos (42,5%) el sangrado fue clasificado como moderado (50-500 ml). En el modelo explicativo transfusión sanguínea en cirugía de canal lumbar estrecho se incluyen: antecedente de cardiopatía (OR 4,68, P 0,034, IC 1,12 – 19,44), Sangrado intraoperatorio >500ml (OR 6,74, p 0,001, 2,09 – 21,74) y >2 niveles intervenidos (OR 3,97, p 0,023, IC 1,20 – 13,09). Conclusión: Como factores asociados a la transfusión sanguínea en el manejo quirúrgico del canal lumbar estrecho a partir de la experiencia de 10 años en la Fundación Santa Fe de Bogotá se encontraron: enfermedad cardiaca, sangrado intraoperatorio mayor de 500ml y más de dos niveles intervenidos.

Prevalencia del síndrome de cementación ósea en pacientes de artroplastia de cadera, Hospital Universitario Mayor Méderi 2014

Resumen Introducción: Con el fin de estimar la prevalencia del síndrome de cementación ósea (SICO) en pacientes llevados a artroplastia de cadera cementada en el Hospital Universitario Mayor Méderi 2014. Materiales y métodos: Se realizó un estudio observacional, descriptivo, de corte transversal, se evaluaron los registros de historia clínica de los pacientes llevados a artroplastia cementada de cadera desde enero a diciembre de 2014. Se estimó la prevalencia del número total de casos de SICO sobre el total de intervenidos y la mortalidad del número de muertes intraoperatorias sobre el total de pacientes que desarrollaron el SICO. Resultados: Se encontraron 102 pacientes llevados a artroplastia cementada de cadera; 73,5% de género femenino, la mediana de edad fue 82 años, la prevalencia de SICO fue de 0,96 x 100 procedimientos y la mortalidad de 7,14 x 100 eventos (1 caso), el evento más frecuentemente relacionado fue las Perdida sanguínea < 300ml (p.valor: 0,006), el resto de diferencias entre los factores de riesgo reconocidos no fueron estadísticamente significativas. Discusión Se encontró una baja frecuencia del evento, con una muerte relacionada, se requieren estudios prospectivos para explorar desenlaces en el tiempo para la presentación de SICO y factores de riesgo adicionales. Palabras clave: "Hipotensión/Diagnóstico", "Prevalencia", "Artroplastia de Reemplazo de Cadera/Efectos Adversos", "Cementos Óseos/Efectos Adversos", "Complicaciones Postoperatorias/Etiología" y "Complicaciones Postoperatorias/Inducido Químicamente"

Surgery after biological therapy in locally advanced NSCLC with molecular driver: feasibility and effectiveness of a new multidisciplinary approach

Introduction: Surgical outcomes after biological therapy have not been investigated yet and no information about timing, postoperative complications and survival have been recorded. Methods: This is a prospective study which compares a group of stage IIIA and IIIB NSCLC patients treated with biological therapy with patients undergoing standard induction chemotherapy. Data reported are preliminary results on the safety and effectiveness of surgery after target therapy. Results: We compared 22 patients treated with standard chemotherapy (Group 1) and 6 patients who received target therapy (Group 2). No differences were observed with an important bias due to the limited number of cases. The median time of resection was 159.8 ± 62.8 for group 1 and 201 ± 57.8 for group 2 (p=0.194). Complete resection was obtained in all Group 1-cases. Post-operative complication rate was 22% vs 16% (p=1). Pathologists reported necrosis >50% in 13% in group 1, Fibrosis >50% was presents respectively in 27% and 33% of patients (p=1). Residual vital tumor was >50% in 77% of patients undergone CT and in 66% of patients undergone TT (p=0.622). A total of 6 (31%) patients in the CT-group developed recurrence, 3 in the TT- group (64.2%), p was 0.634. No difference was observed both in terms of OS (P=0.29, Figure 3) and in term of DFS (P=0.106, Figure 4). Discussion: There is no consensus in the use of target therapy for advanced tumor in association with surgery. EGFR-tyrosine kinase inhibitors showed higher and more rapid response and our study wants to demonstrate that surgery after target therapy gives full access to the advantage of definitive local treatment. In our series, despite fibrosis, radical surgery has been achieved in all patients operated. The intraoperative blood loss, operation time, postoperative hospital stay and postoperative complication rate seems to be similar.

Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis

In multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE), dysfunction of the blood-brain barrier (BBB) leads to edema formation within the central nervous system. The molecular mechanisms of edema formation in EAE/MS are poorly understood. We hypothesized that edema formation is due to imbalanced water transport across the BBB caused by a disturbed crosstalk between BBB endothelium and astrocytes. Here, we demonstrate at the light microscopic and ultrastructural level, the loss of polarized localization of the water channel protein aquaporin-4 (AQP4) in astrocytic endfeet surrounding microvessels during EAE. AQP4 was found to be redistributed over the entire astrocytic cell surface and lost its arrangement in orthogonal arrays of intramembranous particles as seen in the freeze-fracture replica. In addition, immunostaining for the astrocytic extracellular matrix receptor beta-dystroglycan disappeared from astroglial membranes in the vicinity of inflammatory cuffs, whereas immunostaining for the dystroglycan ligands agrin and laminin in the perivascular basement membrane remained unchanged. Our data suggest that during EAE, loss of beta-dystroglycan-mediated astrocyte foot process anchoring to the basement membrane leads to loss of polarized AQP4 localization in astrocytic endfeet, and thus to edema formation in EAE.

Hypercoagulation and hyperkinetic blood pressure indicative of physiological loss-of-control despite behavioural control in Africans: The SABPA study.

OBJECTIVES A dissociation between behavioural (in-control) and physiological parameters (indicating loss-of-control) is associated with cardiovascular risk in defensive coping (DefS) Africans. We evaluated relationships between DefS, sub-clinical atherosclerosis, low-grade inflammation and hypercoagulation in a bi-ethnic sex cohort. METHODS Black (Africans) and white Africans (Caucasians) (n = 375; aged 44.6 ± 9.7 years) were included. Ambulatory BP, vascular structure (left carotid cross-sectional wall area (L-CSWA) and plaque counts), and markers of coagulation and inflammation were quantified. Ethnicity/coping style interaction was revealed only in DefS participants. RESULTS A hypertensive state, less plaque, low-grade inflammation, and hypercoagulation were more prevalent in DefS Africans (27-84%) than DefS Caucasians (18-41%). Regression analyses demonstrated associations between L-CSWA and 24 hour systolic BP (R(2) = 0.38; β = 0.78; p < 0.05) in DefS African men but not in DefS African women or Caucasians. No associations between L-CSWA and coagulation markers were evident. CONCLUSION Novel findings revealed hypercoagulation, low-grade inflammation and hyperkinetic BP (physiological loss-of-control responses) in DefS African men. Coupled to a self-reported in-control DefS behavioural profile, this reflects dissociation between behaviour and physiology. It may explain changes in vascular structure, increasing cerebrovascular disease risk in a state of hyper-vigilant coping.

Chronic Telogen Effluvium And Female Pattern Hair Loss Are Separate And Distinct Forms Of Alopecia: A Histomorphometric And Immunohistochemical Analysis.

Chronic telogen effluvium (CTE), a poorly understood condition, can be confused with or may be a prodrome to female pattern hair loss (FPHL). The pathogenesis of both is related to follicle cycle shortening and possibly to blood supply changes. To analyze a number of histomorphometric and immunohistochemical findings through vascular endothelial growth factor (VEGF), Ki-67, and CD31 immunostaining in scalp biopsies of 20 patients with CTE, 17 patients with mild FPHL and 9 controls. Ki-67 index and VEGF optical density were analyzed at the follicular outer sheath using ImageJ software. CD31 microvessel density was assessed by a Chalkley grid. Significant follicle miniaturization and higher density of nonanagen follicles were found in FPHL, compared with patients with CTE and controls. Ki-67+ index correlated positively with FPHL histological features. The FPHL group showed the highest VEGF optical density, followed by the CTE and control groups. No differences were found in CD31 microvessel density between the three groups. Histomorphometric results establish CTE as a distinct disorder, separate from FPHL from its outset. Its pathogenic mechanisms are also distinct. These findings support the proposed mechanism of 'immediate telogen release' for CTE, leading to cycle synchronization. For FPHL, accelerated anagen follicular mitotic rates and, thus, higher Ki-67 and VEGF values, would leave less time for differentiation, resulting in hair miniaturization.

Understanding Red Blood Cell Parameters In The Context Of The Frailty Phenotype: Interpretations Of The Fibra (frailty In Brazilian Seniors) Study.

Frailty and anemia in the elderly appear to share a common pathophysiology associated with chronic inflammatory processes. This study uses an analytical, cross-sectional, population-based methodology to investigate the probable relationships between frailty, red blood cell parameters and inflammatory markers in 255 community-dwelling elders aged 65 years or older. The frailty phenotype was assessed by non-intentional weight loss, fatigue, low grip strength, low energy expenditure and reduced gait speed. Blood sample analyses were performed to determine hemoglobin level, hematocrit and reticulocyte count, as well as the inflammatory variables IL-6, IL-1ra and hsCRP. In the first multivariate analysis (model I), considering only the erythroid parameters, Hb concentration was a significant variable for both general frailty status and weight loss: a 1.0g/dL drop in serum Hb concentration represented a 2.02-fold increase (CI 1.12-3.63) in an individual's chance of being frail. In the second analysis (model II), which also included inflammatory cytokine levels, hsCRP was independently selected as a significant variable. Each additional year of age represented a 1.21-fold increase in the chance of being frail, and each 1-unit increase in serum hsCRP represented a 3.64-fold increase in the chance of having the frailty phenotype. In model II reticulocyte counts were associated with weight loss and reduced metabolic expenditure criteria. Our findings suggest that reduced Hb concentration, reduced RetAbs count and elevated serum hsCRP levels should be considered components of frailty, which in turn is correlated with sarcopenia, as evidenced by weight loss.

Weight loss associated with exercise training restores ventilatory efficiency in obese children

The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10 +/- 0.2 years; BMI > 95(th) percentile) were randomly divided into two Study groups: D (n=17; BMI = 30 +/- 1 kg/m(2)) and DET (n = 21; 28 +/- 1 kg/m(2)). Ten lean children were included in a control group (10 +/- 0.3 years; 17 +/- 0.5 kg/m(2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO(2) peak). VentE was determined by the VE/VCO(2) method at VAT. Obese children showed lower VO(2) peak and lower VentE than controls (p < 0.05). After interventions, all obese children reduced body weight (p < 0.05). D group did not improve in terms of VO(2) peak or VentE (p > 0.05). In contrast, the DET group showed increased VO(2) peak (p = 0.01) and improved VentE(Delta VE/VCO(2) = -6.1 +/- 0.9; p = 0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants

Objectives This study evaluated the influence of oestrogen deficiency and its therapies on bone tissue around osseointegrated implants. Methods Implants were placed in 66 female rats tibiae. The animals were assigned into five groups: control (CTL), sham, ovariectomy (OVX), oestrogen (EST), and alendronate (ALE). While CTL was sacrificed 60 days after implant placement, other groups were subjected to ovariectomy or sham surgery according to group and euthanized after 90 days. Blood and urine samples were collected at sacrifice day for osteocalcin (OCN) and deoxypyridinoline (DPD) quantification. Densitometry of femur and lumbar vertebrae was performed in order to evaluate rats` skeletal impairment. Non-decalcified sections were referred to fluorescent and light microscopy for analyses of mineral apposition rate (MAR), eroded and osteoclastic surfaces, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO). Results Results from the OVX group showed significantly lower bone mineral density (BMD), BIC, BAFO, and MAR, while OCN, deoxipiridinoline, eroded surface and ostecoclastic surface were increased compared with the other groups of the study. ALE reduced OCN and DPD concentrations, MAR, osteoclastic and eroded surfaces, and no difference was in BIC and BAFO relative to SHAM. EST and CTL showed similar results to SHAM for measurements. Conclusions Oestrogen deficiency exerted a negative influence on bone tissue around implants, while oestrogen replacement therapy and alendronate were effective against its effects. Although alendronate therapy maintained the quantity of bone around implants, studies evaluating bone turnover kinetics are warranted. To cite this article:Giro G, Coelho PG, Pereira RMR, Jorgetti V, Marcantonio E Jr, Orrico SRP. The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants.Clin. Oral Impl. Res. 22, 2011; 259-264.doi: 10.1111/j.1600-0501.2010.01989.x.