ABSTRACT
BACKGROUND: The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension. METHODS: Ninety-four severe sepsis patients with hypotension were randomly assigned to three groups. The patients received the following injections within 15 min at initial treatment: Ns group (n = 32), 5 ml/kg normal saline; Hs group (n = 30), with 5 ml/kg 3.5% sodium chloride; and Sb group (n = 32), 5 ml/kg 5% sodium bicarbonate. Cardiac output (CO), systolic blood pressure, mean arterial pressure (MAP), body temperature, heart rate, respiratory rate and blood gases were measured. RESULTS: There were no differences among the three groups in CO, MAP, heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up, and no significant differences in observed mortality rate after 28 days. However, improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups. Sodium bicarbonate increased the base excess but did not alter blood pH, lactic acid or [HCO3]- values; and neither 3.5% hypertonic saline nor 5% sodium bicarbonate altered the Na+, K+, Ca2+ or Cl- levels. CONCLUSION: All three crystalloid solutions may be used for initial volume loading in severe sepsis, and sodium bicarbonate confers a limited benefit on humans with severe sepsis. TRIAL REGISTRATION: ISRCTN36748319.
Subject(s)
Heart Function Tests , Heart/physiology , Hypotension/drug therapy , Isotonic Solutions/therapeutic use , Sepsis/complications , Adolescent , Adult , Aged , Aged, 80 and over , Blood Chemical Analysis , Blood Gas Analysis , Blood Pressure/drug effects , Body Temperature/drug effects , Cardiac Output/drug effects , Child , Child, Preschool , Crystalloid Solutions , Female , Heart Rate/drug effects , Humans , Isotonic Solutions/administration & dosage , Male , Middle Aged , Pulmonary Ventilation/drug effects , Sepsis/mortalityABSTRACT
PURPOSE: Matrix metalloproteinase-7 (MMP-7) is a member of the MMP family, which is overexpressed by some tumor cells and is thought to enhance the tumor metastatic potential. The aim of this study is to examine the MMP-7 expression in the human colorectal cancer (CRC) liver metastases and normal liver tissue using multiple techniques and to determine its association with liver metastases formation. EXPERIMENTAL DESIGN: MMP-7 mRNA, protein, and enzymatic levels were determined by reverse transcription-PCR, Western blot analysis, and casein zymography in the specimens of human CRC liver metastases and paired normal liver tissue from 44 patients. The cellular localization of MMP-7 was analyzed by immunohistochemistry. RESULTS: Our data reveal that all of the investigated liver metastases samples overexpressed MMP-7 mRNA and protein compared with the normal liver tissue. By zymogram, higher levels of the latent form of MMP-7 were found in 88.6% (39 of 44) liver metastases samples, whereas normal liver tissue exhibited only trace amounts. The activated form of MMP-7 was only found in those in which the pro-MMP-7 was present (n = 39); in contrast, it was not detected in the normal liver tissues. Immunohistochemically, MMP-7 is localized to the cytoplasm of tumor cells, and the strong signal is concentrated in the tumor front areas. CONCLUSIONS: Our observations emphasize the important role of MMP-7 production and activation in human CRC liver metastases formation.
