HSPTX protects against hemorrhagic shock resuscitation-induced tissue injury: an attractive alternative to Ringer's lactate

BACKGROUND: Conventional fluid resuscitation with Ringer's lactated (RL) activates neutrophils and causes end-organ damage. We have previously shown that HSPTX, a combination of small volume hypertonic saline (HS) and pentoxifylline (PTX), a phosphodiesterase-inhibitor, downregulates in vitro neutrophil activation and proinflammatory mediator synthesis. Herein, we hypothesized that HSPTX decreases end-organ injury when compared with RL in an animal model of hemorrhagic shock. METHODS: Sprague-Dawley rats were bled to a mean arterial pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4 mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation. Blood pressure was monitored until the end of resuscitation. Animals were sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF) was obtained for white cell count (total and differential) and TNF-alpha and IL-1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were evaluated by histopathology. Organ damage was graded by a pathologist and a score was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was evaluated by MPO immune staining. RESULTS: There were no differences in mean arterial pressure between groups. At 24 hours, BALF leukocyte count was decreased by 30% in HSPTX animals (p < 0.01). TNF-alpha and IL-1beta levels were markedly decreased in HSPTX-resuscitated animals compared with their RL counterparts (p < 0.01). HSPTX-resuscitated animals (lung injury score = 1.0 +/- 0.4) had markedly decreased acute lung injury compared with RL-treated animals (2.5 +/- 0.3) (p < 0.01). RL resuscitation led to a two-fold increase in lung neutrophil infiltration whereas in HSPTX-treated animals, the number of MPO + cells was similar to sham animals (p < 0.001). Intestinal injury was markedly attenuated by HSPTX (1.1 +/- 0.3) compared with RL animals (2.6 +/- 0.4) (p < 0.001). CONCLUSIONS: HSPTX, a small volume resuscitation strategy with marked immunomodulatory potential led to a marked decrease in end-organ damage. HSPTX is an attractive alternative to RL in hemorrhagic shock resuscitation.     

Comparison of laparoscopic and open partial nephrectomy for duplication anomalies in children

PURPOSE: We compared the outcome of laparoscopic vs open PN for duplication anomalies at our institution. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients undergoing PN within the last 4 years. RESULTS: A total of 34 patients (16 females) were divided into 2 groups. Group 1 consisted of 20 patients undergoing open PN between 2000 and 2003, and group 2 consisted of 14 patients undergoing laparoscopic PN between 2003 and 2004. Mean patient age was 21 months in group 1 and 18 months in group 2. Diagnosis was ectopic ureter in 18 patients, ureterocele in 11, VUR in 4 and ureteropelvic junction obstruction in 1. Cystoscopy was performed as part of the procedure in 30% of the patients in group 1 and 100% of those in group 2. Simultaneous lower tract procedures were performed in 3 patients in group 1 and 2 patients in group 2. Mean duration of PN was 115 minutes for group 1 and 180 minutes for group 2. There was no significant bleeding or need for transfusion except in 1 patient in the open group. Median hospitalization was 3 days for group 1 and 2 days for group 2. Mean analgesic requirement was 2.3 doses of opioids and 2 doses of ketorolac for group 1, and 3.2 doses of opioids for group 2. Acetaminophen only was used in 3 of 20 patients in group 1 and 5 of 14 in group 2. There were 2 complications in each group, namely 1 case of ureteral bleeding and 1 lower pole ureteral injury in group 1, and 1 omental hernia and 1 urinoma in group 2. CONCLUSIONS: Laparoscopic PN is feasible even in small infants, and the results are comparable to the open procedure. Length of hospitalization was shorter in the laparoscopic group. In our series the learning curve for this technique was rapid, and after a few cases the procedure could be done in the same time as open surgery, with the advantages offered by laparoscopy.     

Comparison between the microscope and endoscope in the direct endonasal extended transsphenoidal approach: anatomical study

OBJECT: The authors compare the views afforded by the operating microscope and the endoscope in the direct endonasal extended transsphenoidal approach to the sellar, suprasellar, and parasellar regions. METHODS: Five formalin-fixed, silicone-injected adult cadaveric heads were studied. A direct endonasal transsphenoidal approach was performed via the right nostril, pushing aside the nasal septum. The approach was performed with the microscope first, then with the endoscope. For each step (sellar, suprasellar, and clival), the exposure afforded by direct microscopic view was measured and then compared with that obtained using the endoscope. The direct endonasal approach provides a slightly off-midline view. Although the microscope provides an adequate view of the midline structures and part of the contralateral parasellar areas, the addition of the endoscope allows for a more panoramic view and permits widening of the approach in all directions. CONCLUSIONS: An adequate exposure of the sellar, suprasellar, and infrasellar/upper clival regions can be achieved via a simple, direct endonasal approach. From a direct endonasal route, there is a preferential visualization of the structures contralateral to the approach. The endoscope affords a more panoramic view that extends the area covered by the operating microscope.     

Nonoperative management reduces the overall mortality of grades 3 and 4 blunt liver injuries

Nonoperative (NON-OP) management has been accepted as the treatment of choice for stable patients sustaining blunt liver injury. The objectives were to evaluate the results and changes in the treatment of grades 3 and 4 liver injuries and to determine the impact of NON-OP management on mortality. This was a retrospective review of all grade 3 and 4 blunt liver injuries treated during a 15-year period. One-hundred and twenty-eight consecutive patients (27 NON-OP) were analyzed. Thirty-four patients died in the OP group (33.7%). Nonsurvivors were older (28 versus 39 years), had lower revised trauma score (RTS), higher injury severity score (ISS), and higher transfusion requirements. Six patients failed NON-OP management (22.2%). The mortality rate in the NON-OP group was 0%. NON-OP was associated with a 23.5% reduction in mortality. Unnecessary OP management of grades 3 and 4 liver injuries should be discouraged.     

Plasma kinetics and uptake by the tumor of a cholesterol-rich microemulsion (LDE) associated to etoposide oleate in patients with ovarian carcinoma

OBJECTIVES: Previously, we reported that etoposide oleate associated to a cholesterol-rich microemulsion (LDE) is taken up by malignant cells overexpressing low-density lipoprotein (LDL) receptors. The association is stable, preserves antiproliferative activity of the drug, and reduces toxicity to animals. Here, we determined in patients the plasma kinetics of LDE-etoposide oleate and verified whether the complex concentrates in ovarian carcinomas. METHODS: [(3)H]-etoposide oleate associated to LDE labeled with [(14)C]-cholesteryl oleate was intravenously injected into four ovarian carcinoma patients (50 +/- 8.7 years) 24 h before surgery. Blood samples were collected over a 24-h period to determine the radioactivity plasma decay curves, and the plasma fractional clearance rate (FCR) was calculated by compartmental analysis. Specimens of tumors and normal ovaries excised during the surgery were collected for lipid extraction and radioactive counting. RESULTS: FCRs of LDE label and of the drug were similar (0.0985 and 0.1722, respectively, P = 0.2422). [(14)C]-LDE uptake was 4.9 times and [(3)H]-etoposide oleate uptake was 4.1 times greater in the ovarian tumors than in the contralateral normal ovaries (LDE uptake, in cpm/g = 560 +/- 171 and 146 +/- 59; etoposide oleate uptake = 346 +/- 75 and 103 +/- 56, respectively). CONCLUSIONS: Most of the drug is retained in the microemulsion particles until its removal from the circulation and internalization by the cells. In addition, LDE-etoposide oleate has the ability to concentrate in malignant ovarian tissues. Therefore, the complex may be used to direct and concentrate etoposide oleate in ovarian carcinomas.     

Meconium mineral content in small for gestational age neonates

The mineral concentration of meconia of small for gestational age (SGA) newborns were compared with those of appropriate for gestational age (AGA) newborns of similar gestational ages (GA) to determine whether differences may provide clues of possible nutritional deficits of SGA infants, given that levels of meconium minerals could indicate the use of minerals by the fetus and the sufficiency of the maternal supply of minerals. Twenty-one SGA and 24 AGA newborns were included. Eleven SGA and 15 AGA were < or = 35 weeks GA. Ten SGA and nine AGA infants were > or = 36 weeks GA. All meconia from each neonate was processed and assayed for iron, zinc, copper, manganese, calcium, magnesium, and phosphorus. In the < or = 35-week subgroups, the SGA infants had lower meconium iron and manganese concentrations than that of the AGA. Among > or = 36-week newborns, SGA infants had a higher birthweight-adjusted copper concentration than AGA infants, but no differences were observed for the remaining elements. Lower iron and manganese meconium in < or = 35-week SGA infants may reflect either a greater use or a decreased maternal supply. The higher birthweight-adjusted meconium copper in the > or = 36-week SGA infants may be due to a comparatively reduced fetal use or increased maternal supply. These data may assist in clarifying potential mechanisms affecting intrauterine growth and/or potential nutrient deficits in the neonatal period.