Efectos fisiológicos de una maniobra de reclutamiento alveolar escalonada en pacientes con SDRA en etapa precoz / Physiological effects of a scaled alveolar recruitment maneuver in patients with early-stage acute respiratory distress syndrome

Fundamento. Evaluar el impacto sobre la oxigenación y la distensibilidad del sistema respiratorio, de una maniobra de apertura pulmonar en pacientes con síndrome de distrés respiratorio agudo (SDRA) en etapa temprana de la evolución. Pacientes y método. Estudio llevado a cabo en 18 pacientes con SDRA grave (PaO2/FiO2 < 150 mmHg) y temprano ( 72 h de evolución), a quienes se realizó una maniobra de reclutamiento con valores crecientes de PEEP hasta que ésta alcance 35 cmH2O o una presión máxima en la vía aérea de 60 cmH2O. Resultados. Después de la maniobra, a iguales valores de ventilación controlada por presión y PEEP, mejoró la distensibilidad del sistema respiratorio (32,50 [10,06] frente a 38,07 [11,77] ml/cmH2O; p < 0,001), la PaO2/FiO2 (110,5 [41,09] frente a 217,83 [102,51]; p < 0,001) y aumentó el volumen corriente (6,79 [0,79] a 8,32 [1,33] ml/kg; p < 0,001). Hubo una correlación positiva significativa entre ganancia de volumen corriente y cambio de la PaO2/FiO2 (p = 0,03; intervalo de confianza [IC] del 95 por ciento, 0,044-0,91). Observamos una caída significativa de la presión arterial sistólica (129,94 [23,19] frente a 114,83 [37,12] mmHg; p < 0,001) que mejoró al finalizar la maniobra. No se detectó barotrauma en ningún paciente. Conclusiones. En pacientes con SDRA temprano, ventilados con una estrategia protectora pulmonar, la realización de una maniobra de reclutamiento alveolar fue efectiva en mejorar la oxigenación y la distensibilidad en la mayoría de los pacientes. El aumento de volumen corriente hallado después de la maniobra se correlacionó con la mejoría en la oxigenación (AU)

Immune events associated with the cure of established tumors and spontaneous metastases by local and systemic interleukin 12.

The antitumor activity of recombinant murine interleukin-12 (rIL-12) is documented by a large set of data from numerous mouse models. Because the cellular and molecular mechanisms by which rIL-12 impairs tumor growth are still not fully defined, we compared the effects of local and systemic rIL-12 administration in mice harboring an invasive 7-day-old moderately differentiated and spontaneously metastasizing mammary adenocarcinoma (TSA). Whereas the immune events elicited via the two routes of rIL-12 administration seem to be the same, systemic rIL-12 is markedly more effective; tumor destruction is dependent on a prompt antitumor response resulting from the cooperation of several subsets of reactive cells. The reactions that seem to play a key role are: (a) indirect inhibition of angiogenesis by secondary cytokines (mainly IFN-gamma) and third-level chemokines (inducible protein 10 and monokine induced by IFN-gamma); (b) systemic activation of leukocyte subsets capable of producing proinflammatory cytokines, CTLs, and antitumor antibodies; and (c) destruction of tumor vessels by polymorphonuclear cells. The markedly higher efficacy of systemic rIL-12 seems to rest on its ability to recruit these systemic reactions more quickly and efficiently than local rIL-12.

Comparative brain pathology of HIV-seronegative and HIV-infected drug addicts.

Early stages of infection with human immunodeficiency virus (HIV) were studied in HIV-seropositive drug addicts. Since heroin users are immunocompromized even in the absence of HIV infection, the aim of the present study was to compare the morphological alterations present in HIV-seronegative and HIV-seropositive drug addicts. A total of 60 cases (32 HIV-seronegative subjects, 21 HIV-seropositive patients without signs of acquired immunodeficiency syndrome (AIDS), and 7 HIV-seropositive patients with signs of AIDS) were investigated macroscopically, histologically, and immunohistochemically HIV-seronegative patients presented more frequently with acute drug intoxication, died at a significantly younger age than HIV-seropositive patients, and were found to suffer more frequently from alcohol-related changes. These results indicated that HIV-seronegative and HIV-seropositive patients differed possibly in their drug consumption and also in their general conditions of life. In accordance with previous reports activated microglia and a diffuse astrogliosis in the white matter were detected at a significantly higher frequency and found to be more severe in HIV-seropositive subjects than in HIV-seronegative addicts. A lymphocytic meningitis was present in 6 of 21 HIV-seropositive patients but in none of the HIV-seronegative patients. Perivascular infiltrates consisting of lymphocytes and macrophages were detected at similar frequencies in HIV-seronegative and HIV-seropositive patients but were significantly more severe in patients suffering from lymphocytic meningitis or purulent encephalitis. Opportunistic infections were only demonstrated in 2 AIDS cases. In 10 of the HIV-seronegative patients and in 3 of the HIV-seropositive patients CD68-and Ham56-positive multinucleated cells were detected scattered in the subarachnoidal space exclusively over the frontal cortex.

Pentoxifylline modulation of plasma membrane functions in human polymorphonuclear leukocytes.

Pentoxifylline is known to have major effects on cell membrane function in mammalian cells, including human leukocytes. The protective effects of this agent in animal models of infection and inflammation may be due to alterations in phagocyte (neutrophil and macrophage) function. However, the exact mechanism of action of pentoxifylline is unknown. In this study, we evaluated the effect of the drug on several membrane-associated activities in human polymorphonuclear neutrophils and investigated possible mechanisms for the observed changes in neutrophil function. Pentoxifylline inhibited ingestion of microbial particles (Staphylococcus aureus and zymosan); decreased superoxide generation activated by zymosan, formyl-methionyl-leucyl-phenylalanine, and concanavalin A (but not phorbol myristate acetate); and decreased uptake (transport) of adenosine stimulated by formyl-methionyl-leucyl-phenylalanine and zymosan. In contrast, pentoxifylline actually increased clindamycin uptake in zymosan-stimulated polymorphonuclear neutrophils. However, pentoxifylline had no effect on uptake of adenosine or clindamycin in unstimulated neutrophils. In comparison with known inhibitors of nucleoside transport (nitrobenzylthioinosine and dipyridamole), the results suggested that pentoxifylline does not bind to membrane nucleoside transport receptors. At concentrations which inhibit neutrophil function, pentoxifylline activity is not mediated through external membrane nucleoside regulatory sites. Thus, pentoxifylline affects the activation signal chain at a point beyond the membrane receptors. Whatever its precise mechanism of action, pentoxifylline has a striking modulatory effect on cell membrane-associated responses in stimulated leukocytes and may prove useful for control of injurious inflammatory states.

Somatostatina en el tratamiento de emergencia de la hemorragia digestiva alta en hipertensos portales / Somatostatin in the emergency treatment of upper digestive hemorrhage in patients with portal hypertension

Durante un período de 2 años se evaluó utilidad de la somatostatina (250 mcg en bolo seguido de 250 mcg/h IV) en 17 episodios de hemorragia por várices esofágicas (VES) y 7 por lesiones agudas de la mucosa gastroduodenal (LAMG) en hipertensos portales diagnosticados por endoscopía de urgencia. Se obtuvo la hemostásia inicial (dentro de las 2 hs.) en el 76% de las VES y el 100% de las LAMG. Tres de los 4 pacientes con VES y los 2 con LAMG que recidivaron la hemorragia durante el tratamiento respondieron al duplicar la dosis de somatostatina. La hemostasia a las 24 hs., fue del 71% para las VES, iniciándose en ese momento la esclerosis endoscópica, y del 100% ára las LAMG. Con las combinación de distintas terapéuticas se controló la hemorragia en 16 de los 17 pacientes com VES (94%). En ningún caso se observaron efectos colaterales adjudicables a la somatostatina. De acuerdo a nuestros hallazgos la somatostatina es una opción terapéutica valiosa en el tratamiento de emergencia de la hemorragia digestiva alta en pacientes con hipertensión portal

Somatostatina en el tratamiento de emergencia de la hemorragia digestiva alta en hipertensos portales / Somatostatin in the emergency treatment of upper digestive hemorrhage in patients with portal hypertension

Durante un período de 2 años se evaluó utilidad de la somatostatina (250 mcg en bolo seguido de 250 mcg/h IV) en 17 episodios de hemorragia por várices esofágicas (VES) y 7 por lesiones agudas de la mucosa gastroduodenal (LAMG) en hipertensos portales diagnosticados por endoscopía de urgencia. Se obtuvo la hemostásia inicial (dentro de las 2 hs.) en el 76% de las VES y el 100% de las LAMG. Tres de los 4 pacientes con VES y los 2 con LAMG que recidivaron la hemorragia durante el tratamiento respondieron al duplicar la dosis de somatostatina. La hemostasia a las 24 hs., fue del 71% para las VES, iniciándose en ese momento la esclerosis endoscópica, y del 100% ára las LAMG. Con las combinación de distintas terapéuticas se controló la hemorragia en 16 de los 17 pacientes com VES (94%). En ningún caso se observaron efectos colaterales adjudicables a la somatostatina. De acuerdo a nuestros hallazgos la somatostatina es una opción terapéutica valiosa en el tratamiento de emergencia de la hemorragia digestiva alta en pacientes con hipertensión portal (AU)

[Somatostatin in the emergency treatment of upper digestive hemorrhage in patients with portal hypertension]. / Somatostatina en el tratamiento de emergencia de la hemorragia digestiva alta en hipertensos portales.

During a 2-yr period 15 patients (17 episodes) with variceal bleeding (VB) and 7 with cirrhosis and acute gastroduodenal haemorrhage (GDH) received intravenous somatostatin (250 mcg per hr after a bolus of 250 mcg). Initial control of bleeding was achieved in 13 (76%) with VB and in all with GDH. Three of the 4 patients with VB and 2 with GDH who rebled during treatment were controlled increasing the infusion to 500 mcg/hr. Patients with VB received somatostatin for 24 hrs, time selected for initiating injection sclerotherapy, and those with GDH for 48-72 hrs. At 24 hrs 71% of patients with VB and all with GDH were free of bleeding. Combining different therapies VB was controlled in 16 of the 17 episodes (94%) with only one death. No complications were observed in any of the 22 patients treated.

Somatostatina en el tratamiento de emergencia de la hemorragia digestiva alta en hipertensos portales. / [Somatostatin in the emergency treatment of upper digestive hemorrhage in patients with portal hypertension]

During a 2-yr period 15 patients (17 episodes) with variceal bleeding (VB) and 7 with cirrhosis and acute gastroduodenal haemorrhage (GDH) received intravenous somatostatin (250 mcg per hr after a bolus of 250 mcg). Initial control of bleeding was achieved in 13 (76

) with VB and in all with GDH. Three of the 4 patients with VB and 2 with GDH who rebled during treatment were controlled increasing the infusion to 500 mcg/hr. Patients with VB received somatostatin for 24 hrs, time selected for initiating injection sclerotherapy, and those with GDH for 48-72 hrs. At 24 hrs 71

of patients with VB and all with GDH were free of bleeding. Combining different therapies VB was controlled in 16 of the 17 episodes (94

) with only one death. No complications were observed in any of the 22 patients treated.