Placental programmed cell death: insights into the role of aquaporins.

STUDY HYPOTHESIS: Are the placental aquaporins (AQPs) involved in the apoptosis of human trophoblast? STUDY FINDING: The general blocking of placental AQPs with HgCl2 and, in particular, the blocking of AQP3 activity with CuSO4 abrogated the apoptotic events of human trophoblast cells. WHAT IS KNOWN ALREADY: Although apoptosis of trophoblast cells is a natural event involved in the normal development of the placenta, it is exacerbated in pathological processes, such as pre-eclampsia, where an abnormal expression and functionality of placental AQPs occur without alterations in the feto-maternal water flux. Furthermore, fluctuations in O2 tension are proposed to be a potent inducer of placental apoptotic changes and, in explants exposed to hypoxia/reoxygenation (H/R), transcellular water transport mediated by AQPs was undetectable. This suggests that AQPs might be involved in processes other than water transport, such as apoptosis. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Explants from normal term placentas were maintained in culture under conditions of normoxia, hypoxia and H/R. Cell viability was determined by assessing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide incorporation. For the general or specific inhibition of AQPs, 0.3 mM HgCl2, 5 mM CuSO4, 0.3 mM tetraethylammonium chloride (TEA) or 0.5 mM phloretin were added to the culture medium before explants were exposed to each treatment. Oxidative stress parameters and apoptotic indexes were evaluated in the presence or absence of AQPs blockers. AQP3 expression was confirmed by western blot and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: First, we observed that in H/R treatments cell viability decreased by 20.16 ± 5.73% compared with those explants cultured in normoxia (P = 0.009; n = 7). Hypoxia did not modify cell viability significantly. Both hypoxia and H/R conditions induced oxidative stress. Spontaneous chemiluminescence and thiobarbituric acid reactive substance levels were significantly increased in explants exposed to hypoxia (n = 6 per group, P = 0.0316 and P = 0.0009, respectively) and H/R conditions (n = 6 per group, P = 0.0281 and P = 0.0001, respectively) compared with those cultured in normoxia. Regarding apoptosis, H/R was a more potent inducer of trophoblast apoptosis than hypoxia alone. Bax expression and the number of apoptotic nuclei were significantly higher in explants cultured in H/R compared with normoxia and hypoxia conditions (n = 12, P = 0.0135 and P = 0.001, respectively). DNA fragmentation was only observed in H/R and, compared with normoxia and hypoxia, the activity of caspase-3 was highest in explants cultured in H/R (n = 12, P = 0.0001). In explants exposed to H/R, steric blocking of AQP activity with HgCl2 showed that DNA degradation was undetectable (n = 12, P = 0.001). Bax expression and caspase-3 activity were drastically reduced (n = 12, P = 0.0146 and P = 0.0001, respectively) compared with explants cultured in H/R but not treated with HgCl2. Similar results were observed in explants exposed to H/R when we blocked AQP3 activity with CuSO4. DNA degradation was undetectable and the number of apoptotic nuclei and caspase-3 activity were significantly decreased compared with explants cultured in H/R but not treated with CuSO4 (n = 12, P = 0.001 and P = 0.0001, respectively). However, TEA and phloretin treatments, to block AQP1/4 or AQP9, respectively, failed in abrogate apoptosis. In addition, we confirmed the expression and localization of AQP3 in explants exposed to H/R. LIMITATIONS, REASONS FOR CAUTION: Our studies are limited by the number of experimental conditions tested, which do not fully capture the variability in oxygen levels, duration of exposure and alternating patterns of oxygen seen in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that any alteration in placental AQP expression might disturb the equilibrium of the normal apoptotic events and may be an underlying cause in the pathophysiology of placental gestational disorders such as pre-eclampsia. Furthermore, the dysregulation of placental AQPs may be one of the crucial factors in triggering the clinical manifestations of pre-eclampsia. LARGE SCALE DATA: n/a. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by UBACyT 20020090200025 and 20020110200207 grants and PIP-CONICET 11220110100561 grant, and the authors have no conflict of interest to declare.

Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways.

INTRODUCTION: The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. METHODS: To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. RESULTS: In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. DISCUSSION: Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface.

Effects of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure.

The effect of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) has been reported by several investigators, without any consensus being reached. Acute neurological and neurosurgical patients suffer intracranial hypertension and acute lung injury with hypoxemia. Since PEEP may improve hypoxemia but elevate ICP and decrease CPP, it is important to determine the influence of varying levels of PEEP on ICP and CPP. The aim of the study was to investigate the changes in ICP and CPP associated with different levels of PEEP. Twenty patients requiring ICP monitoring and mechanical ventilation were enrolled. Patients had severe head injury (n = 10), spontaneous intracerebral haemorrhage (n = 5), and subarachnoid haemorrhage (n = 5). PEEP was raised from 5 (basal) to 15 cm H2O in steps of 5 cm H2O. After at least 10 minutes of each new PEEP setting, ICP and CPP were measured. PEEP at 10 and 15 cm H2O produced a significant (p < 0.05) increase in intracranial pressure 11.6 +/- 5.6 and 14.6 +/- 6.28 mm Hg, respectively; no significant (p = 0.819) change occurred in CPP.

[Early release of the antiinflammatory cytokine IL-10 in traumatic brain injury]. / Liberación precoz de la citokina antiinflamatoria IL10 en el trauma severo de cráneo.

It has been reported that upwards of 50% of patients who survive an initial brain traumatic insult subsequently die due to infection and multiple organ failure. A paralysis of cell-mediated immunity following trauma, partially induced by anti-inflammatory cytokine release, appears to be responsible for the increased susceptibility to infections. We determined the plasma levels of the anti-inflammatory cytokine IL-10 and the pro-inflammatory TNF-alpha in 15 patients admitted with severe traumatic brain injury (TBI). None of the patients had received glucocorticoid or catecholamine treatment. Thirteen volunteers served as controls. At study entry the IL-10 plasma levels were significantly higher than in controls: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p < 0.001 (Mann-Whitney test). There was no difference between the first (at study entry) and second sample (4 hours later) (Wilcoxon test). TNF-alpha plasma levels were similar in patients and controls at study entry and 4 hours later. We conclude that severe TBI patients present an early response, with a significant increase of IL-10 plasma levels. These results could partially explain the immunodepression following TBI.

[Acute pancreatitis. Our experience]. / Pancreatitis aguda. Nuestra experiencia.

Between the years 1975 and 1984, 228 patients with acute pancreatitis (A.P.) have been studied at the "A. Posadas Hospital". The diagnosis was confirmed in 212 patients by surgery, in the remaining 16 by clinical evaluation, increase in the activity of serum or peritoneal fluid amylase, ultra-sonography and computed tomography. The sex distribution was: female 151 (66.2%) male 77 (33.8%), the mean age in each group was 42.9 and 45 years respectively. The etiologic factors were: biliary tract disease 178 (78%) alcohol 24 (10.5%) idiopathic 16 (7%) others factors 10 (4.4%). We found mild and moderate forms of the illness in 179 (78.5%) and severe form in 49 (21.5%) patients. The mortality rate of the whole group was 29 (12.7%) and according to the etiology it was, in the biliary group 20 (11.2%) alcoholic 4 (16.6%) idiopathic 3 (18.7%). The mortality in the mild and moderate forms was 5% and 40.8% in the severe forms. The patients who underwent surgery were classified in three groups according to the opportunity of surgical treatment: elective surgery, early surgery, surgery for complications. There was no mortality in the elective surgery group. The patients operated on early period had a mortality of 18.75% (21 pts.) whereas those operated due to complications had a mortality of 42.1% (8 pts.). According to the above mentioned experience we consider that a patient with an A.P. must be classified with the known indexes in mild or severe forms, at the same time one should study the actual etiologic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of patients with acute pancreatitis (AP), (1984-1994) decade. Comparison with a past series]. / Análisis de pacientes con pancreatitis aguda (PA), Década (1984-1994). Comparación con serie anterior.

Between 1984-1994 records of 190 patients with acute pancreatitis (AP) were reviewed. Diagnosis was confirmed by surgery in 141, by necropsy 1 (75%), and for the remaining patients, by CT and clinical evaluation. Female 122 were female (64%), male 68 (36%), mean age 41 years (range 7-82 years). The etiologic factors were gallstones in 129 (68%) with 4 deaths (3%), alcoholic in 26 (14%) with 5 (19%) deaths, idiopathic in 24 (13%) and miscellaneous 11 (5%), the last 2 without mortality. The overall mortality was 5% (9/190). Surgical treatment was indicated in 141 (74%) and endoscopic treatment in 2 (1%), 47 patients (25%) received only medical treatment. One-hundred and fifty-four patients (81%) were mild forms with a Ranson mean score 2.2 without mortality. In this group, emergency surgery was indicated in 7 (6%), early in 3 (3%), late in 1 (0.9%) and elective in 99 (90%). In the severe group were 36 patients (19%) with a mean Ranson score of 4.2. Nine patients died (25%), 31 were surgically treated, by emergency surgery in 17 (47%), 1 (3%) early surgery and 13 (36%) late surgery. The mortality rate of this group was compared with previous series of the same hospital (1975-1984 series). The 1984-1994 group showed a significant overall mortality decrease 4.7% vs 12.7% (p = 0.0047); 3.1% vs 11.2% (p = 0.0087) for the gallstones group; without mortality in the idiopathic and miscellaneous form compared with 18.7% and 20% respectively of the previous series; no mortality was observed in the mild AP compared with 5% of the previous series. The mortality in the severe form was 25% vs 40.8% (1975-1984 group). We consider that the decreased mortality could be attributed to the improvement in the diagnosis, early recognition of the severe forms, systemic supportive care in the severe forms, the use of antibiotics with wide spectrum and deeper penetration in the pancreas and specially in the change of the surgical timing. Although, in the first period the option was the early pancreatic surgery, in the second this was indicated only in particular cases.

Oxygen tension modulates AQP9 expression in human placenta.

UNLABELLED: Placental hypoxia has been implicated in pregnancy pathologies such as preeclampsia. We have previously reported that AQP9 is highly expressed in syncytiotrophoblast from normal placentas and shows an overexpression in preeclamptic placentas, with a lack of functionality for water transport. Up to now, the response of AQP9 to changes in the oxygen tension in trophoblast cells is still unknown. OBJECTIVE: Our aim was to establish whether alterations in oxygen levels may modulate AQP9 expression in human placenta. METHODS: A theoretical analysis of the human AQP9 gene to find conserved DNA regions that could serve as putative HIF-1 binding sites. Then, explants from normal placentas were cultured at different concentrations of oxygen or with 250 µM CoCl2. AQP9 molecular expression and water uptake was determined. RESULTS: Fourteen consensus HIF-1 binding sites were found in the human AQP9 gene, but none of them in the promoter region. However, placental AQP9 decreased abruptly when HIF-1α is expressed by deprivation of oxygen or CoCl2 stabilization. In contrast, after reoxygenation, HIF-1α was undetectable while AQP9 increased significantly and changed its cellular distribution, showing the same pattern as that previously described in preeclamptic placentas. Accordingly with the decrease in AQP9 expression, water uptake decreased in explants exposed to hypoxia or treated with CoCl2. Conversely as we expected, after reoxygenation, water uptake decreased dramatically compared to the control and was not sensitive to HgCl2. CONCLUSION: Our findings suggest that oxygen tension may modulate AQP9 expression in human placenta. However, the role of AQP9 still remains uncertain.

Ventilator-associated pneumonia due to colistin susceptible-only microorganisms.

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.

Intoxicación barbitúrica grave / Dangerous barbituric intoxication

Se realizó un estudio retrospectivo con los objetivos de establecer la prevalencia de la intoxicación barbitúrica grave en un servicio de Terapia Intensiva, conocer la incidencia de complicaciones y la mortalidad, y evaluar el tratamiento utilizado. Se analizaron 15 pacientes, la mayoría jóvenes y de sexo femenino. Se registraron 19 episodios de complicaciones. El 86 por ciento de los pacientes se hallaba en coma al ingreso (escala de Glasgow < 8). El deterioro hemodinámico se observó en el 46,7 por ciento de los casos, y el 60 por ciento requirió ventilación mecánica. El protocolo de tratamiento incluyó: 1) Diálisis intestinal (utilización de carbón activado y de purgantes salinos con el objetivo de lograr catarsis en las primeras 48 hs del tratamiento); 2) Diuresis alcalina; 3) Sostén de funciones vitales. La mortalidad fue del 13 por ciento. Conclusión: Evitar el lavado gástrico, iniciar precozmente el protocolo de diálisis intestinal y realizar hemodiálisis sólo si aquélla fracasa, durante las primeras 24 hs

Pancreatitis aguda: nuestra experiencia / Acute pancreatitis: our experience

Se estudiaron 228 pacientes con pancreatitis aguda internados en el Hospital Nacional Prof. A. Posadas, entre los años 1975-1984. El diagnóstico se confirmó en 212 por cirugía y en los restantes 16 por el cuadro clínico, elevación de amilasa en suero y líquido peritoneal; ecografía y tomografia computada. Pertenecieron al sexo femenino 151 (66,2%), al masculino 77 (33,8%) con edad promedio de 42,9 y 45 años respectivamente. La etiología fue: Patología biliar 178 (78%)alcohólica 24 (10,5%) idiopática 16 (7%) otros factores 10 (4,4%). La mortalidad global fue de 29 pacientes (12,7%) que correspondieron a la etiología biliar 20 (11,2%) alcohólica idiopática 3 (18,7%). La mortalidad en las formas leves y moderadas fue 5% (T. 3) y en la severa 40,8% (T. 4). Los pacientes operados fueron clasificados en tres grupos de acuerdo al tiempo de realización del acto quirúrgico: 1) cirugía electiva; 2) cirugía precoz; 3) cirugía por complicaciones. No hubo mortalidad en los pacientes operados electivamente. En los operados en forma precoz fue de 18,75% (21 pacientes) mientras que los operados por complicaciones fue de 42,1% (8 pacientes) (T. 5). De acuerdo a la experiencia recogida consideramos que una vez diagnosticada una P. A. debe clasificarse con los índices conocidos, en formas leves y graves y simultáneamente debe estudiarse el factor causal presente. Las formas leves o moderadas son tratadas médicamente con el esquema clásico, manteniendo la vigilancia hasta su evolución clínica, momento en el cual, si se trata una P. A. biliar, pasa a cirugía electiva dentro de la misma internación. Las formas graves P.A.N. se tratan médicamente en Terapia Intensiva, por un equipo médico-quirúrgico si la evolución es satisfactoria, la conducta será similar a la anterior, si la evolución es desfavorable se deben poner en marcha todos los medios diagnósticos para demostrar la presencia de complicaciones que pueden exigir una cirugía de urgencia como las necrosis pancreáticas y peri-pancreáticas extensas y en especial la sepsis, que son los factores que desconpensan a éstos pacientes. La cirugía dentro de las primeras 48 horas, sólo la indicamos por duda diagnóstica u obstrucción biliar irreductible, especialmente, si coexiste con infección biliar: colangitis o colecistitis aguda

Pancreatitis aguda: nuestra experiencia / Acute pancreatitis: our experience

Se estudiaron 228 pacientes con pancreatitis aguda internados en el Hospital Nacional Prof. A. Posadas, entre los años 1975-1984. El diagnóstico se confirmó en 212 por cirugía y en los restantes 16 por el cuadro clínico, elevación de amilasa en suero y líquido peritoneal; ecografía y tomografia computada. Pertenecieron al sexo femenino 151 (66,2%), al masculino 77 (33,8%) con edad promedio de 42,9 y 45 años respectivamente. La etiología fue: Patología biliar 178 (78%)alcohólica 24 (10,5%) idiopática 16 (7%) otros factores 10 (4,4%). La mortalidad global fue de 29 pacientes (12,7%) que correspondieron a la etiología biliar 20 (11,2%) alcohólica idiopática 3 (18,7%). La mortalidad en las formas leves y moderadas fue 5% (T. 3) y en la severa 40,8% (T. 4). Los pacientes operados fueron clasificados en tres grupos de acuerdo al tiempo de realización del acto quirúrgico: 1) cirugía electiva; 2) cirugía precoz; 3) cirugía por complicaciones. No hubo mortalidad en los pacientes operados electivamente. En los operados en forma precoz fue de 18,75% (21 pacientes) mientras que los operados por complicaciones fue de 42,1% (8 pacientes) (T. 5). De acuerdo a la experiencia recogida consideramos que una vez diagnosticada una P. A. debe clasificarse con los índices conocidos, en formas leves y graves y simultáneamente debe estudiarse el factor causal presente. Las formas leves o moderadas son tratadas médicamente con el esquema clásico, manteniendo la vigilancia hasta su evolución clínica, momento en el cual, si se trata una P. A. biliar, pasa a cirugía electiva dentro de la misma internación. Las formas graves P.A.N. se tratan médicamente en Terapia Intensiva, por un equipo médico-quirúrgico si la evolución es satisfactoria, la conducta será similar a la anterior, si la evolución es desfavorable se deben poner en marcha todos los medios diagnósticos para demostrar la presencia de complicaciones que pueden exigir una cirugía de urgencia como las necrosis pancreáticas y peri-pancreáticas extensas y en especial la sepsis, que son los factores que desconpensan a éstos pacientes. La cirugía dentro de las primeras 48 horas, sólo la indicamos por duda diagnóstica u obstrucción biliar irreductible, especialmente, si coexiste con infección biliar: colangitis o colecistitis aguda (AU)

Pancreatitis aguda. Nuestra experiencia. / [Acute pancreatitis. Our experience]

Between the years 1975 and 1984, 228 patients with acute pancreatitis (A.P.) have been studied at the [quot ]A. Posadas Hospital[quot ]. The diagnosis was confirmed in 212 patients by surgery, in the remaining 16 by clinical evaluation, increase in the activity of serum or peritoneal fluid amylase, ultra-sonography and computed tomography. The sex distribution was: female 151 (66.2

) male 77 (33.8

), the mean age in each group was 42.9 and 45 years respectively. The etiologic factors were: biliary tract disease 178 (78

) alcohol 24 (10.5

) idiopathic 16 (7

) others factors 10 (4.4

). We found mild and moderate forms of the illness in 179 (78.5

) and severe form in 49 (21.5

) patients. The mortality rate of the whole group was 29 (12.7

) and according to the etiology it was, in the biliary group 20 (11.2

) alcoholic 4 (16.6

) idiopathic 3 (18.7

). The mortality in the mild and moderate forms was 5

and 40.8

in the severe forms. The patients who underwent surgery were classified in three groups according to the opportunity of surgical treatment: elective surgery, early surgery, surgery for complications. There was no mortality in the elective surgery group. The patients operated on early period had a mortality of 18.75

(21 pts.) whereas those operated due to complications had a mortality of 42.1

(8 pts.). According to the above mentioned experience we consider that a patient with an A.P. must be classified with the known indexes in mild or severe forms, at the same time one should study the actual etiologic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Liberación precoz de la citokina antiinflamatoria IL10 en el trauma severo de cráneo. / [Early release of the antiinflammatory cytokine IL-10 in traumatic brain injury]

It has been reported that upwards of 50

of patients who survive an initial brain traumatic insult subsequently die due to infection and multiple organ failure. A paralysis of cell-mediated immunity following trauma, partially induced by anti-inflammatory cytokine release, appears to be responsible for the increased susceptibility to infections. We determined the plasma levels of the anti-inflammatory cytokine IL-10 and the pro-inflammatory TNF-alpha in 15 patients admitted with severe traumatic brain injury (TBI). None of the patients had received glucocorticoid or catecholamine treatment. Thirteen volunteers served as controls. At study entry the IL-10 plasma levels were significantly higher than in controls: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p < 0.001 (Mann-Whitney test). There was no difference between the first (at study entry) and second sample (4 hours later) (Wilcoxon test). TNF-alpha plasma levels were similar in patients and controls at study entry and 4 hours later. We conclude that severe TBI patients present an early response, with a significant increase of IL-10 plasma levels. These results could partially explain the immunodepression following TBI.

Inmunoglobulina (ig) polivalente en el tratamiento de la sepsis abdominal / Polyvalent immunoglobulin (Ig) in the treatment of intraabdominal sepsis

La sepsis grave mantiene una elevada mortalidad en los últimos 40 años. Múltiples intentos por moderar la respuesta inflamatoria sistémica, mediante la infusión de inmunoglobulinas (Ig), han demostrado resultados controvertidos. Los diferentes criterios de diagnóstico, la diferente población en estudio y reducido número de pacientes, dificultan obtener conclusiones definitivas. Objetivo: Evaluar si la infusión de Ig mejora la evolución de pacientes con sepsis abdominal. Lugar: 7 unidades de Cuidados Intensivos Polivalentes. Diseño: Estudio multicéntrico, prospectivo, randomizado, doble ciego. Intervenciones: Los pacientes fueron asignados aleatoriamente para recibir Ig (Grupo A: GA) o placebo (Grupo B: GB) conjuntamente con el tratamiento habitual de la sepsis abdominal. Resultado: Treinta y siete pacientes fueron incluidos en el estudio. 20 en el GA y 17 en el GB. El nivel medio de APACHE II, TISS, las disfunciones y fallas orgánicas no fueron diferentes entre los grupos. La mortalidad general fue del 16,7 por ciento, superior en el GB (26 por ciento) respecto del GA (5 por ciento) aunque tal diferencia no alcanzó significación estadística. Conclusiones: Nuestros hallazgos sugieren, que la infusión de Ig (Pentaglobin) en pacientes con sepsis abdominal con foco resuelto, reduce la mortalidad al alta de la UCI. Nuevos estudios clínicos son necesarios para confirmar los presentes hallazgos (AU)

Intoxicación barbitúrica grave / Dangerous barbituric intoxication

Se realizó un estudio retrospectivo con los objetivos de establecer la prevalencia de la intoxicación barbitúrica grave en un servicio de Terapia Intensiva, conocer la incidencia de complicaciones y la mortalidad, y evaluar el tratamiento utilizado. Se analizaron 15 pacientes, la mayoría jóvenes y de sexo femenino. Se registraron 19 episodios de complicaciones. El 86 por ciento de los pacientes se hallaba en coma al ingreso (escala de Glasgow < 8). El deterioro hemodinámico se observó en el 46,7 por ciento de los casos, y el 60 por ciento requirió ventilación mecánica. El protocolo de tratamiento incluyó: 1) Diálisis intestinal (utilización de carbón activado y de purgantes salinos con el objetivo de lograr catarsis en las primeras 48 hs del tratamiento); 2) Diuresis alcalina; 3) Sostén de funciones vitales. La mortalidad fue del 13 por ciento. Conclusión: Evitar el lavado gástrico, iniciar precozmente el protocolo de diálisis intestinal y realizar hemodiálisis sólo si aquélla fracasa, durante las primeras 24 hs (AU)

Inmunoglobulina (ig) polivalente en el tratamiento de la sepsis abdominal / Polyvalent immunoglobulin (Ig) in the treatment of intraabdominal sepsis

La sepsis grave mantiene una elevada mortalidad en los últimos 40 años. Múltiples intentos por moderar la respuesta inflamatoria sistémica, mediante la infusión de inmunoglobulinas (Ig), han demostrado resultados controvertidos. Los diferentes criterios de diagnóstico, la diferente población en estudio y reducido número de pacientes, dificultan obtener conclusiones definitivas. Objetivo: Evaluar si la infusión de Ig mejora la evolución de pacientes con sepsis abdominal. Lugar: 7 unidades de Cuidados Intensivos Polivalentes. Diseño: Estudio multicéntrico, prospectivo, randomizado, doble ciego. Intervenciones: Los pacientes fueron asignados aleatoriamente para recibir Ig (Grupo A: GA) o placebo (Grupo B: GB) conjuntamente con el tratamiento habitual de la sepsis abdominal. Resultado: Treinta y siete pacientes fueron incluidos en el estudio. 20 en el GA y 17 en el GB. El nivel medio de APACHE II, TISS, las disfunciones y fallas orgánicas no fueron diferentes entre los grupos. La mortalidad general fue del 16,7 por ciento, superior en el GB (26 por ciento) respecto del GA (5 por ciento) aunque tal diferencia no alcanzó significación estadística. Conclusiones: Nuestros hallazgos sugieren, que la infusión de Ig (Pentaglobin) en pacientes con sepsis abdominal con foco resuelto, reduce la mortalidad al alta de la UCI. Nuevos estudios clínicos son necesarios para confirmar los presentes hallazgos

Analisis de pacientes con pancreatitis aguda (PA), decada (1984-1994) comparacion con serie anterior / Analysis of patients with acute pancreatitis (AP), (1984-1994) comparation with serie anterior

Se revisaron las historias clínicas de 190 pacientes internados entre 1984 y 1994 con diagnóstico de pancreatitis aguda. Tuvieron confirmación quirúrgica 141, necrópsica 1 (75 por ciento), y las restantes confirmadas por la evolución clínica y TAC. El sexo femenino 122 (64 por ciento), masculino 68 (36 por ciento), media de edad de 41 años (mínima 7, máxima 82). La etiología fue biliar en 129 (68 por ciento) con 4 fallecidos (3 por ciento), alcohólica en 26 (14 por ciento), con 5 fallecidos (19 por ciento), idiopática en 24 (13 por ciento) y miscelánea 11 (5 por ciento), las dos últimos sin mortalidad. La mortalidad global fue del 5 por ciento (9/190). Se efectuó tratamiento quirúrgico en 141 (74 por ciento) y endoscópico en 2 (1 por ciento), 47 pacientes (25 por ciento) no fueron operados. El grupo PA leve estuvo conformado por 154 pacientes (81 por ciento) con un score de Tanson promedio de 2.2 y sin mortalidad. Se indicó cirugía de urgencia en 7 (6 por ciento), temprana en 3 (3 por ciento), tardía en 1 (0,9 por ciento) u programada en 99 (90 por ciento). En el grupo de PA grave hubo 36 pacientes (19 por ciento) con un score promedio de Ranson de 4.2. Fallecieron 9 (25 por ciento). Se operaron 31 pacientes, de estos 17 (47 por ciento) de urgencia, 1 (3 por ciento) cirurgía temprana y 13 (36 por ciento) tardía. Se compararon las cifras de mortalidad de este grupo, con otra serie del mismo Hospital entre 1975-1984. Comparando los dos series se observó en el grupo 1984-1994: disminución significativa de la mortalidad global 4.7 por ciento vs 12.7 por ciento (p=0.0047); en la mortalidad de la etiologia biliar 3.1 por ciento vs 11.2 por ciento (p=0.0087); sin mortalidad en las etiologías idiopáticas y miscelánea, comparada 18.7 por ciento y 20 por ciento respectivamente de la serie anterior; mortalidad nula de la PA leve comparada con el 5 por ciento de la serie anterior y por último de la PA leve comparada con el 5 por ciento de la serie anterior y por último la mortalidad en la forma grave fue menor 25 por ciento vs 40.8 por ciento. Consideramos como causa de este avance mejor diagnóstico, evaluación temprana de la severidad, medidas de apoyo sistémico en las formas graves, la administración de antibióticos de mayor espectro y penetración en el páncreas y especialmente el cambio en el tiempo de indicación quirúrgica. Mientras que en el primer período se optó por la cirurgía temprana sobre el páncreas, en el segundo se indicó intervención diferida, salvo en casos especiales.

Analisis de pacientes con pancreatitis aguda (PA), decada (1984-1994) comparacion con serie anterior / Analysis of patients with acute pancreatitis (AP), (1984-1994) comparation with serie anterior

Se revisaron las historias clínicas de 190 pacientes internados entre 1984 y 1994 con diagnóstico de pancreatitis aguda. Tuvieron confirmación quirúrgica 141, necrópsica 1 (75 por ciento), y las restantes confirmadas por la evolución clínica y TAC. El sexo femenino 122 (64 por ciento), masculino 68 (36 por ciento), media de edad de 41 años (mínima 7, máxima 82). La etiología fue biliar en 129 (68 por ciento) con 4 fallecidos (3 por ciento), alcohólica en 26 (14 por ciento), con 5 fallecidos (19 por ciento), idiopática en 24 (13 por ciento) y miscelánea 11 (5 por ciento), las dos últimos sin mortalidad. La mortalidad global fue del 5 por ciento (9/190). Se efectuó tratamiento quirúrgico en 141 (74 por ciento) y endoscópico en 2 (1 por ciento), 47 pacientes (25 por ciento) no fueron operados. El grupo PA leve estuvo conformado por 154 pacientes (81 por ciento) con un score de Tanson promedio de 2.2 y sin mortalidad. Se indicó cirugía de urgencia en 7 (6 por ciento), temprana en 3 (3 por ciento), tardía en 1 (0,9 por ciento) u programada en 99 (90 por ciento). En el grupo de PA grave hubo 36 pacientes (19 por ciento) con un score promedio de Ranson de 4.2. Fallecieron 9 (25 por ciento). Se operaron 31 pacientes, de estos 17 (47 por ciento) de urgencia, 1 (3 por ciento) cirurgía temprana y 13 (36 por ciento) tardía. Se compararon las cifras de mortalidad de este grupo, con otra serie del mismo Hospital entre 1975-1984. Comparando los dos series se observó en el grupo 1984-1994: disminución significativa de la mortalidad global 4.7 por ciento vs 12.7 por ciento (p=0.0047); en la mortalidad de la etiologia biliar 3.1 por ciento vs 11.2 por ciento (p=0.0087); sin mortalidad en las etiologías idiopáticas y miscelánea, comparada 18.7 por ciento y 20 por ciento respectivamente de la serie anterior; mortalidad nula de la PA leve comparada con el 5 por ciento de la serie anterior y por último de la PA leve comparada con el 5 por ciento de la serie anterior y por último la mortalidad en la forma grave fue menor 25 por ciento vs 40.8 por ciento. Consideramos como causa de este avance mejor diagnóstico, evaluación temprana de la severidad, medidas de apoyo sistémico en las formas graves, la administración de antibióticos de mayor espectro y penetración en el páncreas y especialmente el cambio en el tiempo de indicación quirúrgica. Mientras que en el primer período se optó por la cirurgía temprana sobre el páncreas, en el segundo se indicó intervención diferida, salvo en casos especiales. (AU)