The pathophysiological impact of intra-abdominal hypertension in pigs.

BACKGROUND: Intra-abdominal hypertension and abdominal compartment syndrome are common with clinically significant consequences. We investigated the pathophysiological effects of raised IAP as part of a more extensive exploratory animal study. The study design included both pneumoperitoneum and mechanical intestinal obstruction models. METHODS: Forty-nine female swine were divided into six groups: a control group (Cr; n = 5), three pneumoperitoneum groups with IAPs of 20mmHg (Pn20; n = 10), 30mmHg (Pn30; n = 10), 40mmHg (Pn40; n = 10), and two mechanical intestinal occlusion groups with IAPs of 20mmHg (MIO20; n = 9) and 30mmHg (MIO30; n = 5). RESULTS: There were significant changes (p<0.05) noted in all organ systems, most notably systolic blood pressure (SBP) (p<0.001), cardiac index (CI) (p = 0.003), stroke volume index (SVI) (p<0.001), mean pulmonary airway pressure (MPP) (p<0.001), compliance (p<0.001), pO2 (p = 0.003), bicarbonate (p = 0.041), hemoglobin (p = 0.012), lipase (p = 0.041), total bilirubin (p = 0.041), gastric pH (p<0.001), calculated glomerular filtration rate (GFR) (p<0.001), and urine output (p<0.001). SVV increased progressively as the IAP increased with no obvious changes in intravascular volume status. There were no significant differences between the models regarding their impact on cardiovascular, respiratory, renal and gastrointestinal systems. However, significant differences were noted between the two models at 30mmHg, with MIO30 showing worse metabolic and hematological parameters, and Pn30 and Pn40 showing a more rapid rise in creatinine. CONCLUSIONS: This study identified and quantified the impact of intra-abdominal hypertension at different pressures on several organ systems and highlighted the significance of even short-lived elevations. Two models of intra-abdominal pressure were used, with a mechanical obstruction model showing more rapid changes in metabolic and haematological changes. These may represent different underlying cellular and vascular pathophysiological processes, but this remains unclear.

Amniotic Membrane Restores Chronic Wound Features to Normal in a Keratinocyte TGF-ß-Chronified Cell Model.

Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-ß (TFG-ß) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-ß1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation at later stages. Interestingly, when checking the gene expression of markers known to be altered in TGF-ß chronified cells and involved in cell cycle regulation, early migratory responses, senescence, and chronic inflammation, we discovered that AM treatment seemed to reset back to keratinocyte status. The analysis of the evolution of both the levels of keratinocyte activation marker cytokeratin 17 and the spatial-temporal expression pattern of the proliferation marker Ki-67 in human in vivo biopsy samples suggests that responses to AM recorded in TGF-ß chronified HaCaT cells would be homologous to those of resident keratinocytes in chronic wounds. All these results provide further evidence that sustained TGF-ß might play a key role in wound chronification and postulate the validity of our TGF-ß chronified HaCaT in vitro model for the study of chronic wound physiology.

Prophylactic use of incisional negative pressure wound therapy for the prevention of surgical site occurrences in general surgery: Consensus document.

BACKGROUND: Surgical site occurrences pose a threat to patient health, potentially resulting in significant increases in health care spending caused by using additional resources. The objective of this study was to reach a consensus among a group of experts in incisional negative pressure wound therapy to determine the indications for using this type of treatment prophylactically and to analyze the associated risk factors of surgical site occurrences in abdominal surgery. METHODS: A group of experts in incisional negative pressure wound therapy from Spain and Portugal was formed among general surgery specialists who frequently perform colorectal, esophagogastric, or abdominal wall surgery. The Coordinating Committee performed a bibliographic search to identify the most relevant publications and to create a summary table to serve as a decision-making protocol regarding the use of prophylactic incisional negative pressure wound therapy based on factors related to the patient and type of procedure. RESULTS: The patient risk factors associated with surgical site occurrence development such as age, immunosuppression, anticoagulation, hypoalbuminemia, smoking, American Society of Anesthesiologists classification, diabetes, obesity, and malnutrition were analyzed. For surgical procedure factors, surgical time, repeated surgeries, organ transplantation, need for blood transfusion, complex abdominal wall reconstruction, surgery at a contaminated site, open abdomen closure, emergency surgery, and hyperthermic intraperitoneal chemotherapy were analyzed. CONCLUSION: In our experience, this consensus has been achieved on a tailored set of recommendations on patient and surgical aspects that should be considered to reduce the risk of surgical site occurrences with the use of prophylactic incisional negative pressure wound therapy, particularly in areas where the evidence base is controversial or lacking.

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.

Corrigendum: Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

[This corrects the article DOI: 10.3389/fimmu.2019.01151.].

Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

Cryopreserved amniotic membrane in the treatment of diabetic foot ulcers: a case series.

OBJECTIVE: The amniotic membrane (AM) is a tissue with low immunogenity and high therapeutic potential due to its anti-inflammatory, anti-fibrotic and antimicrobial effects. This paper describes the use of cryopreserved amniotic membrane allografts to treat diabetic foot ulcers (DFUs) in patients with diabetes. METHOD: In this case series, AM was processed to obtain a final medicinal product: cryopreserved amniotic membrane. cryopreserved AM was applied every 7-10 days until total epithelialisation of the DFUs. RESULTS: A total of 14 patients with DFUs (median size: 12.30cm, (range: 0.52-42.5cm2) were treated and followed up until complete closure (median time: 20 weeks, range: 7-56 weeks). Patients received 4-40 AM applications. All patients in this study achieved complete epithelialisation of the wound. No adverse events were observed. CONCLUSION: AM is a feasible and safe treatment in complex DFUs. Furthermore, the treatment is successful in achieving epithelialisation of long-evolution, unhealed wounds resistant to conventional therapies.

Intestinal histopathological changes in a porcine model of pneumoperitoneum-induced intra-abdominal hypertension.

BACKGROUND: Low splanchnic perfusion is an immediate effect of pneumoperitoneum-induced intra-abdominal hypertension (IAH). Anatomical structure results in the intestinal mucosa being the area most sensitive to hypoperfusion. The relationship between intestinal injury and clinical parameters of tissue perfusion [abdominal perfusion pressure (APP), gastric intramucosal pH (pHi) and lactic acid (Lc)] has not been previously studied. This study aimed to monitorize intestinal pathogenesis through sequential ileal biopsies and to measure APP, pHi, and Lc levels at different pneumoperitoneum-induced intra-abdominal pressures (20, 30, and 40 mmHg) to evaluate the potential relationships between them. MATERIALS AND METHODS: Fifty pigs were divided into four groups; a control group (C) and three experimental groups with different pneumoperitoneum-induced levels [20 mmHg (G20), 30 mmHg (G30), and 40 mmHg (G40)], that were maintained for 3 and 5 h. APP, pHi, and Lc were measured and ileal biopsies taken laparoscopically every 30 min. The mucosal damage was graded using the standardized Park's Score and animals were classified as injured (I+) or uninjured (I-). RESULTS: Different histopathological lesions were observed in groups G20, G30, and G40 but no damage observed in group C. A 33.3% of animals in G20 and G30 were I+ after 3 h, while 93.3% were injured in G40. After 5 h, histopathological lesions were no longer seen in some animals in G20 and only 10% were I+. Conversely, in G30 I+ pigs increased to 80% while those in G40 remained at 93.3% I+. The I+ animals had significantly lower APP and pHi than those I-. Lc was the clinical parameter that showed the earliest differences, with significantly higher figures in I+ animals. CONCLUSIONS: The evolution of intestinal injuries from pneumoperitoneum-induced IAH depends on the degree of IAP. These damages may be associated with decreases in APP and pHi, and increases in Lc.

Time-course evaluation of intestinal structural disorders in a porcine model of intra-abdominal hypertension by mechanical intestinal obstruction.

BACKGROUND: A mechanical intestinal obstruction (MIO) can generate intraabdominal hypertension (IAH) that is life threatening. The intestines are very sensitive to IAH since the low splanchnic perfusion causes intestinal hypoxia, local acidosis and bacterial translocations. This may lead to acute intestinal distress syndrome (AIDS). The identification of intestinal injuries during IAH and its correlation with clinical parameters as the abdominal perfusion pressure (APP), the gastric intramucosal pH (pHi) and lactic acid (Lc) are still unknown. This study aimed to evaluate the sequence of intestinal histopathological findings in an MIO model and to analyze potential relationships with parameters currently used in clinical practice (APP, pHi and Lc). MATERIAL AND METHODS: Twenty pigs were divided into three groups: a control group (n = 5) and two experimental groups with 20 mmHg (G1, n = 10) and 30 mmHg (G2, n = 5) of IAH by MIO. The pressures were maintained for 3 hours, except in 5 animals in G1 where it was maintained for 5 hours. The APP, pHi and LA were recorded and biopsies of the terminal ileum were taken every 30 minutes in all groups. The intestinal damage was graded according to the Park Score. RESULTS: Intestinal injuries were found in 42.9% of pigs in the experimental groups. The lesions were independent of the level and duration of IAH. Although APP and pHi were slightly lower in injured animals (I +) of G1 and G2, there were no significant differences among those uninjured (I-). Lc was significantly increased in all I+ pigs from the onset of IAH. CONCLUSION: The IAH by MIO causes intestinal lesions from the first 30 minutes with concurrent decreases in APP and pHi and increases in Lc. Lc could be the best clinical parameter related to intestinal damages with a clear difference between I + and I- animals.

Amniotic membrane stimulates cell migration by modulating transforming growth factor-ß signalling.

Keratinocyte migration is a mandatory aspect of wound healing. We have previously shown that amniotic membrane (AM) applied to chronic wounds assists healing through a process resulting in the overexpression of c-Jun at the wound's leading edge. We have also demonstrated that AM modifies the genetic programme induced by transforming growth factor-ß (TGF-ß) in chronic wounds. Here we used a scratch assay of mink lung epithelial cells (Mv1Lu) and a spontaneously immortalized human keratinocyte cell line (HaCaT) cells to examine the influence of AM application on the underlying signalling during scratch closure. AM application induced c-Jun phosphorylation at the leading edge of scratch wounds in a process dependent on MAPK and JNK signalling. Strikingly, when the TGF-ß-dependent Smad-activation inhibitor SB431542 was used together with AM, migration improvement was partially restrained, whereas the addition of TGF-ß had a synergistic effect on the AM-induced cell migration. Moreover, antagonizing TGF-ß with specific antibodies in both cell lines or knocking out TGF-ß receptors in Mv1Lu cells had similar effects on cell migration as using SB431542. Furthermore, we found that AM was able to attenuate TGF-ß-Smad signalling specifically at the migrating edge; AM treatment abated Smad2 and Smad3 nuclear localization in response to TGF-ß in a process dependent on mitogen-activated protein kinase kinase 1 (MEK1) activation but independent of EGF receptor or JNK activation. The involvement of Smad signalling on AM effects on HaCaT keratinocytes was further corroborated by overexpression of either Smad2 or Smad3 and the use of Smad phosphorylation-specific inhibitors, revealing a differential influence on AM-induced migration for each Smad. Thus, AM TGF-ß-Smad signalling abating is essential for optimal cell migration and wound closure.

Amniotic membrane promotes focal adhesion remodeling to stimulate cell migration.

During wound healing, the migration of keratinocytes onto newly restored extracellular matrix aims to reestablish continuity of the epidermis. The application of amniotic membrane (AM) to chronic, deep traumatic, non-healing wounds has proven successful at stimulating re-epithelialization. When applied on epithelial cell cultures, AM activates extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases 1/2 (JNK1/2), with the overexpression and phosphorylation of c-Jun along the wound edge. The effect of AM on the migration of cells was investigated by studying critical proteins involved in the focal adhesions turn-over: Focal Adhesion Kinase (FAK), Paxillin and Vinculin. In Mv1Lu and HaCaT cells, validated models for cell migration and wound healing, AM affected the expression and activation of Paxillin, but did not affect Vinculin expression, both factors which integrate into focal adhesions. Moreover, AM regulation also affected FAK activity through phosphorylation. Finally, we have determined that AM regulation of focal adhesions involves both JNK and MEK MAP kinase signaling pathways. This data provides a molecular background to understand how AM regulates critical cell and molecular aspects of cell migration, organizing and directing the movement of cells by the continuous formation, maturation, and turnover of focal adhesion structures at the migration leading edge.

Amniotic membrane application for the healing of chronic wounds and ulcers.

Wound healing usually follows a predictable sequence and prognosis of events. Its evolutionary process is the result of a complicated interaction between patient-related factors, the wound, the treatment used and the skills and knowledge of the professionals who treat them. Only through a meticulous initial assessment of the wound is it possible to identify the factors that contribute to its complexity. The challenge for professionals will be to implement efficient therapies at the right time and in the most cost-efficient way in order to reduce associated problems, treat the symptoms and expectations of the patients and achieve adequate wound healing whenever possible. This is particularly evident in big chronic wounds with considerable tissue loss, which become senescent in the process of inflammation or proliferation losing the ability to epithelialize. Generally, chronic wounds do not respond to current treatments, therefore they need special interventions. AM is a tissue of particular interest as a biological dressing and it has well-documented reepithelialization effects which are in part related to its capacity to synthesize and release biological active factors. Our studies have demonstrated that amniotic membrane (AM) is able to induce epithelialization in chronic wounds that were unable to epithelialize. AM induces several signaling pathways that are involved in cell migration and/or proliferation. Additionally, AM is able to selectively antagonize the anti-proliferative effect of transforming growth factor-ß (TGF-ß) by modifying the genetic program that TGF-ß induces on keratinocytes. The combined effect of AM on keratinocytes, promoting cell proliferation/migration and antagonizing the effect of TGF-ß is the perfect combination, allowing chronic wounds to move out of their non-healing state and progress into epithelialization.

Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds.

BACKGROUND: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. METHODS AND FINDINGS: To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. CONCLUSIONS: The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation.

Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application.

Epithelial and mesenchymal cells isolated from the amniotic membrane (AM) possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases.

Hipertensión intraabdominal: consecuencias sobre la circulación esplácnica. Estudio preliminar en un modelo de ascitis / Intra-abdominal hypertension: Effects on the splanchnic circulation. Preliminary study in a model of ascites

INTRODUCCIÓN: La hipertensión intraabdominal se define como una elevación de la presión intraabdominal que da lugar a una disfunción progresiva de los órganos intraabdominales. Objetivo Estudiar las consecuencias de la hipertensión intraabdominal a nivel esplácnico en un modelo porcino determinando la medida indirecta de elección. Material y métodos Se utilizaron 10 cerdos divididos en un grupo control y en un grupo de presión de 20 mmHg con un modelo de ascitis. Se registraron las presiones intraabdominal transvesical y transperitoneal, calculándose el grado de correlación entre ambas. Se obtuvo el ácido láctico, la alanina aminotransferasa, la glucosa y el pH intramucoso gástrico. Se determinó la presión arterial media y la presión de perfusión abdominal, observando la correlación de esta con el pH intramucoso gástrico y el ácido láctico. Los parámetros se registraron durante 3 h. Resultados Hubo una alta correlación entre ambas presiones (R2 = 0,98). A 20 mmHg el ácido láctico aumentó significativamente entre grupos a los 180 min (p < 0,011). El pH intramucoso gástrico mostró diferencias significativas entre grupos desde el inicio (p = 0,004) descendiendo significativamente a partir de los 120 min. La presión arterial media y la perfusión abdominal disminuyeron progresivamente apreciándose cambios significativos más precoces en la presión de perfusión abdominal (p = 0,001) mostrando una buena correlación con los parámetros estudiados. No hubo afectación significativa de los parámetros hepáticos. Conclusiones Consideramos la presión intraabdominal transvesical como la técnica de elección, siendo la presión de perfusión abdominal un marcador sensitivo de la hipertensión intraabdominal y el pH intramucoso gástrico el parámetro más precozmente afectado

INTRODUCTION: Intra-abdominal hypertension is defined as a rise in intra-abdominal pressure leading to progressive dysfunction of the abdominal organs. OBJECTIVE: To evaluate the effects of intra-abdominal hypertension on the splanchnic circulation in a porcine animal model with a view to determining the diagnostic method of choice. MATERIAL AND METHODS: A total of 10 swine were divided into 2 groups: a control group and a group with an ascites pressure of 20 mmHg. Transvesical and transperitoneal intra-abdominal pressures were registered, and the correlation between the measurements obtained was determined. Concentrations of lactic acid, alanine aminotransferase, glucose and gastric mucosal pH were also obtained. We registered the mean arterial and abdominal perfusion pressures, and the correlation of the latter with gastric mucosal pH and lactic acid concentrations. The parameters were registered for a total of 3 hours. RESULTS: We observed a high correlation between transvesical and transperitoneal measurements of intra-abdominal pressure (R2 = 0.98). In the 20 mmHg pressure group, lactic acid concentrations increased significantly at 180 min (p < 0.011). Gastric mucosal pH differed significantly between the 2 groups from the beginning of the study (p = 0.004) and significantly decreased from 120 min onward. Mean arterial and abdominal perfusion pressures gradually decreased during the trial, with early significant changes in the abdominal perfusion pressure (p = 0.001), and a good correlation with the remaining study parameters. There were no significant changes in hepatic indicators. CONCLUSIONS: We believe the transvesical approach to be the technique of choice to determine intra-abdominal pressure. Abdominal perfusion pressure is a sensitive marker of intra-abdominal hypertension, and gastric mucosal pH is the first parameter to be affected

[Intra-abdominal hypertension: effects on the splanchnic circulation. Preliminary study in a model of ascites]. / Hipertensión intraabdominal: consecuencias sobre la circulación esplácnica. Estudio preliminar en un modelo de ascitis.

INTRODUCTION: Intra-abdominal hypertension is defined as a rise in intra-abdominal pressure leading to progressive dysfunction of the abdominal organs. OBJECTIVE: To evaluate the effects of intra-abdominal hypertension on the splanchnic circulation in a porcine animal model with a view to determining the diagnostic method of choice. MATERIAL AND METHODS: A total of 10 swine were divided into 2 groups: a control group and a group with an ascites pressure of 20mmHg. Transvesical and transperitoneal intra-abdominal pressures were registered, and the correlation between the measurements obtained was determined. Concentrations of lactic acid, alanine aminotransferase, glucose and gastric mucosal pH were also obtained. We registered the mean arterial and abdominal perfusion pressures, and the correlation of the latter with gastric mucosal pH and lactic acid concentrations. The parameters were registered for a total of 3hours. RESULTS: We observed a high correlation between transvesical and transperitoneal measurements of intra-abdominal pressure (R(2)=0.98). In the 20mmHg pressure group, lactic acid concentrations increased significantly at 180min (p<0.011). Gastric mucosal pH differed significantly between the 2 groups from the beginning of the study (p=0.004) and significantly decreased from 120min onward. Mean arterial and abdominal perfusion pressures gradually decreased during the trial, with early significant changes in the abdominal perfusion pressure (p=0.001), and a good correlation with the remaining study parameters. There were no significant changes in hepatic indicators. CONCLUSIONS: We believe the transvesical approach to be the technique of choice to determine intra-abdominal pressure. Abdominal perfusion pressure is a sensitive marker of intra-abdominal hypertension, and gastric mucosal pH is the first parameter to be affected.

El método clínico: evaluación de acciones para fortalecerlo desde la asignatura Medicina Comunitaria en la carrera de Medicina / The Clinical Method: Actions Evaluation to Strengthen it from Community Medicine Subject of Medicine Career

Introducción: la relación médico paciente es el eslabón más sensible y humano de la práctica médica de todos los tiempos y el interrogatorio su principal instrumento; es evidente el deterioro en la aplicación del método clínico y ello compromete la formación de los estudiantes.Objetivo: evaluar la aplicación del método clínico en los estudiantes del tercer año de medicina posterior a aplicación de la estrategia de vinculación básico-clínica en la asignatura de Medicina Comunitaria del segundo año de la carrera, a partir de los resultados de sus exámenes prácticos de la asignatura de Medicina Interna. Métodos: se estudió la efectividad de la aplicación de una estrategia utilizada en la asignatura de Medicina Comunitaria del segundo año de la carrera) para elevar el conocimiento y aplicación del método clínico en los estudiantes del tercer año de la carrera de Medicina de la Facultad de Ciencias Médicas Mariana Grajales Coello de la Universidad Ciencias Médicas de Holguín, en el curso 2011-2012. El universo estuvo constituido por todos los estudiantes de este año de la carrera que se presentaron al examen práctico y se conformó una muestra intencional donde estuvieron incluidas las áreas de salud con mejores resultados en los exámenes y se consultaron los resultados de la promoción según áreas en las dos cursos para proceder a su comparación.Resultados: el 50 por ciento de los estudiantes obtuvieron mejores resultados en los exámenes prácticos y las deficiencias descendieron desde 95 por ciento en el interrogatorio en el curso anterior a 18,9 por ciento en el curso actual, mientras que en el examen físico de 92 por ciento descendió a 24,5 por ciento. El 46,7 por ciento de los profesores identificaron un mejor accionar en los estudiantes contra el 20 por ciento antes antes de aplicar la estrategia evaluada(AU)...

Introduction: the doctor-patient relationship is the most sensitive and human one in the medical practice of all time and questionnaire is its main instrument, it is obvious on the lack of the use of clinical method and it influence on the students´ formation.Objective: to evaluate the clinical method application in third year students of medicine after implementation of the strategy of basic clinical link in the subject of Community Medicine of the second year of this career, considering the results obtained by these students in the practical examination in Internal Medicine subject.Methods: the effectiveness of the implementation of a strategy used in the subject of Community Medicine of the second year of the career to improve the clinical method knowledge and its application in the third year students at Mariana Grajales Coello Faculty of Medical Science of Medical University of Holguín in ,2011-2012, The universe consisted of all students of the third year of the career that passed the practical examination, and the sample comprised those who obtained the better results in this examination considering the health areas in order to establish comparison among them.Results: ,50 percent, of students achieved better results in practical examination and the previous deficiencies decreased from 95% to ,18.9 percent, in the current year, while in the physical examination it decreased from ,92 percent, to ,24.5 percent, 46.7 percent, of teachers observed better results in students before the strategy was applied.Conclusions: the strategy improved clinical method application by the students. The teachers noted an improvement in the relationship between the different stages of implementation, although the promotion results were similar in both courses(AU)...

Tonometry as a predictor of inadequate splanchnic perfusion in an intra-abdominal hypertension animal model.

BACKGROUND: The gastrointestinal system is the most sensitive to the presence of intra-abdominal hypertension. We aimed to assess the early prognostic value of gastric air tonometry as a predictor of inadequate splanchnic perfusion and determine its relation with abdominal perfusion pressure (APP). METHODS: Twenty-five Large White swine were used for this study. A control group and two study groups were included, in which intra-abdominal pressure (IAP) was elevated with Co2 to 20 and 30 mmHg during 5 h. We measured the intramucosal gastric pH (pHim) and determined gastric luminal PCO2 (PgCO2) and PgCO2gap (gastric luminal CO2-arterial CO2) to evaluate gastric acidity. APP was indirectly obtained through IAP and mean arterial pressure. Additionally, histopathologic samples of small intestine were obtained and analyzed. RESULTS: pHim showed a decrease in IAP groups, with statistical significance in the 30 mmHg group, 90 min after stabilization period (P < 0.01). Serum lactate showed delayed alteration when compared with pHim, with significant increase, 180 min after stabilization (P < 0.05). The values of PgCO2 and PCO2gap were increased in IAP groups, being statistically significant in the 30 mmHg group, 120 and 150 min, respectively, after stabilization. In increased IAP groups, there was a time progressive decrease of APP, with statistically significant differences observed between groups at 20 min (P < 0.001). The histopathology study revealed parenchymal injury of the intestine at 30 mmHg. CONCLUSIONS: Tonometry is sensitive to the increase in IAP and relates to the reduction of APP generated by splanchnic hypoperfusion.