Four-dimensional Computed Tomography (4DCT) for Preoperative Localization of Parathyroid Adenomas.

BACKGROUND: Four-dimensional parathyroid computed tomography (4DCT) is a relatively new parathyroid imaging technique that provides functional and highly detailed anatomic information about parathyroid tumors. OBJECTIVES: To assess the accuracy of 4DCT for the preoperative localization of parathyroid adenomas (PTAs) in patients with biochemically confirmed primary hyperparathyroidism (PHPT) and a history of failed surgery or unsuccessful localization using 99mTc-sestamibi scanning and ultrasonography. METHODS: Between January 2013 and January 2015, 55 patients with PHPT underwent 4DCT at Hillel Yaffe Medical Center, Hadera, Israel. An initial unenhanced scan was followed by an IV contrast injection of nonionic contrast material (120 ml of at 4 ml/s). Scanning was repeated 25, 60, and 90 seconds after the initiation of IV contrast administration. An experienced radiologist blinded to the earlier imaging results reviewed the 4DCT for the presence and location (quadrant) of the suspected PTAs. At the time of the study, 28 patients had undergone surgical exploration following 4DCT and we compared their scans with the surgical findings. RESULTS: 4DCT accurately localized 96% (27/28) of abnormal glands, all of which were hypervascular and showed characteristic rapid enhancement on 4DCT that could be distinguished from Level II lymph nodes. Surgery found hypovascular cystic PTA in one patient who produced a negative 4DCT scan. All patients had solitary PTAs. The scan at 90 seconds provided no additional information and was abandoned during the study. CONCLUSIONS: 4DCT accurately localized hypervascular parathyroid lesions and distinguished them from other tissues. A three-phase scanning protocol may suffice.

[PARATHYROID AUTOTRANSPLANTATION IN ADULTS AND CHILDREN].

INTRODUCTION: The indications and methods of parathyroid autotransplantation in children and adults are reviewed, with special emphasis on the methods of immediate transplantation and delayed autotransplantation after cryopreservation. Parathyroid autotransplantation is performed during surgery when all four parathyroid glands have been intentionally resected in parathyroid hyperplasia, or when all four glands were inadvertently damaged during total thyroidectomy, or recurrent neck surgery. When parathyroid damage is suspected during thyroid or extensive neck surgery, cryopreservation of a parathyroid gland is performed. If future signs and symptoms of hypoparathyroidism develop with low blood calcium and PTH levels, then the cryopreserved gland is transplanted into the arm muscles. The maximum effective time that the parathyroid can be cryopreserved is two years. The major postoperative causes of permanent hypoparathyroidism, where parathyroid autotransplantation is indicated are: primary and secondary parathyroid hyperplasia, extensive or repeated neck surgeries which include thyroid surgery and large goiter or retrosternal goiter, particularly in children. The success rate of autotransplantation in preventing postoperative hypoparathyroidism reported in the literature is highly variable, and is dependent on timing, disease, and duration of tissue storage. Although preservation of parathyroid glands in situ at surgery is desirable, parathyroid autotransplantation during thyroidectomy virtually eliminates postoperative hypoparathyroidism. Parathyroid autotransplantation must be performed in dedicated endocrine surgical centers that have had extensive experience in performing this procedure in both children and adults.

[MINIMALLY INVASIVE PARATHYROIDECTOMY (MIP) UNDER LOCAL ANESTHESIA FOR TREATMENT OF PRIMARY HYPERPARATHYROIDISM (PHPT) CAUSED BY A SINGLE ADENOMA].

INTRODUCTION: Minimally Invasive Parathyroidectomy (MIP) has become the treatment of choice of Primary Hyperparathyroidism (PHPT) caused by an adenoma. In the present investigation we describe our experience with MIP performed under local anesthesia. METHODS: MIP was performed on 454 of 496 patients (91.5%) with PHPT. In 170 patients (37.4%), MIP was accomplished under local anesthesia. This procedure was elected when the medical condition prohibited general anesthesia, or in accordance with the patient's request. RESULTS: MIP under local anesthesia for PHPT was accomplished in 162 (95.3%) of the patients. In 8 patients the procedure was converted to general anesthesia, while the adenoma was located in 5 of these patients. In 3 patients (1.8%) the adenoma was not located even under general anesthesia and they awaited further investigations. Fifteen patients (8.2%) developed temporary hoarseness, and 20 patients (11.8%) developed temporary hypocalcemia postoperatively. CONCLUSIONS: MIP under local anesthesia for PHPT caused by an adenoma is feasible and safe, with a success rate of 95.3% similar to MIP performed under general anesthesia. MIP under local anesthesia has not yet become a prevalent procedure worldwide, as well as in our country. The results of the present study support our conclusions for utilizing this method under local anesthesia.

Negative Fine-Needle Aspiration in Patients with Goiter: Should We Doubt It?

BACKGROUND: Epidemiologic studies demonstrated higher incidence of thyroid cancer in patients with multinodular goiters compared to the general population. The aim of this study was to evaluate the risk of finding significant thyroid cancer in patients undergoing thyroidectomy for presumed benign disease. METHODS: The records of 273 patients operated for indications other than cancer or indeterminate cytology were reviewed and analyzed. RESULTS: 202 (74%) patients had a preoperative fine-needle aspiration (FNA) performed. FNA was benign in 96% of patients and non-diagnostic in 4%. Malignancy was unexpectedly found in 50 (19%) patients. Papillary carcinoma constituted 94% of cancers and 86% of cancers were incidental microcarcinomas. Only 7 (2.6%) patients of the entire cohort had tumors greater than 1 cm, of those only 3 had a previous benign FNA (false-negative rate 1.5%). CONCLUSIONS: The rate of significant thyroid cancer found unexpectedly in resected goiters is extremely low. A negative FNA excludes significant cancer with near certainty.

Parathyroid surgery in the elderly: should minimally invasive surgery be abandoned?

BACKGROUND: Single adenoma is the cause of 80 % of primary hyperparathyroidism (PHPT) resulting in wide acceptance of minimally invasive parathyroidectomy (MIP). The incidence of PHPT increases with age. Little information is available regarding the prevalence of multiglandular disease (MGD) in older patients. METHODS: The records of 537 patients that underwent parathyroid surgery between January 2005 and October 2012 at two endocrine surgery referral centers were retrospectively reviewed. Comparison was performed between patients younger than 65 and older than 65 years of age. Clinical variables included preoperative laboratories and imaging, extent of neck exploration, number of glands excised, and intraoperative parathyroid hormone levels during surgery. RESULTS: There were 374 (70 %) patients in the younger age group (YG) and 163 (30 %) patients in the older age group (OG). The mean age was 50 ± 0.5 and 71 ± 0.4 years, respectively. There was no difference between the groups in terms of gender or laboratory results. MGD was significantly more common in the OG (24 % vs. 12 %; p = 0.001) and similarly MIP was less commonly completed in the OG (49 % vs. 68 %; p < 0.001). Cure rates were comparable between the OG and YG (93 % vs. 95 %; p = 0.27). In the OG, patients with MGD had significantly smaller glands as compared to patients with single adenomas in this group (331 ± 67 vs. 920 ± 97 mg; p = 0.006, respectively). CONCLUSIONS: MGD in PHPT was found to be more prevalent in older patients. Planning a bilateral neck exploration should be considered in older patients, especially when a relatively small gland is suggested by imaging or encountered during surgery.

Fresh Frozen Plasma Increases Hemorrhage in Blunt Traumatic Brain Injury and Uncontrolled Hemorrhagic Shock.

BACKGROUND: Blunt traumatic brain injury (bTBI) and uncontrolled hemorrhagic shock (UCHS) are common causes of mortality in polytrauma. We studied the influence of fresh frozen plasma (FFP) resuscitation in a rat model with both bTBI and UCHS before achieving hemorrhage control. METHODS: The bTBI was induced by an external weight drop (200 g) onto the bare skull of anesthetized male Lewis (Lew/SdNHsd) rats; UCHS was induced by resection of two-thirds of the rats' tails. Fifteen minutes following trauma, bTBI+UCHS rats underwent resuscitation with FFP or lactated Ringer's solution (LR). Eight groups were evaluated: (1) Sham; (2) bTBI; (3) UCHS; (4) UCHS+FFP; (5) UCHS+LR; (6) bTBI+UCHS; (7) bTBI+UCHS+FFP; and (8) bTBI+UCHS+LR. Bleeding volume, hematocrit, lactate, mean arterial pressure (MAP), heart rate, and mortality were measured. RESULTS: The study included 97 rats that survived the immediate trauma. Mean blood loss up to the start of resuscitation was similar among UCHS only and bTBI+UCHS rats (P=0.361). Following resuscitation, bleeding was more extensive in bTBI+UCHS+FFP rats (5.2 mL, 95% confidence interval [CI] 3.7, 6.6) than in bTBI+UCHS+LR rats (2.5 mL, 95% CI 1.2, 3.8) and bTBI+UCHS rats (1.9 mL, 95% CI 0, 3.9) (P=0.005). Overall mortality increased if bleeding was above 4.5 mL (92.3% versus 8%; P<0.001). Mortality was 83.3% (10/12) in bTBI+UCHS+FFP rats, 41.7% (5/12) in bTBI+UCHS+LR rats, and 64.3% (9/14) in bTBI+UCHS rats. CONCLUSION: The bTBI did not exacerbate bleeding in rats undergoing UCHS. Compared to LR, FFP resuscitation was associated with a significantly increased blood loss in bTBI+UCHS rats.

[Minimally invasive parathyroidectomy for treatment of primary hyperparathyroidism caused by parathyroid adenoma].

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is frequently used for the treatment of primary hyperparathyroidism (PHPT) caused by a single adenoma. This method depends on preoperative localization of the tumor by a sestamibi scan, cervical ultrasound, and intraoperative parathyroid hormone (PTH) measurements. When the sestamibi scan is negative, the classical 4-gland exploration is used instead of MIP. AIMS: a. To evaluate the effectiveness of MIP for treatment of PHPT caused by adenoma. b. To evaluate the use of PTH selective venous sampling (PTH-SVS) in patients with negative sestamibi scintigraphy. METHODS: MIP was performed in all patients in whom an adenoma was diagnosed by sestamibi scan and US. When the sestamibi scan was negative, PTH-SVS was performed preoperatively for localization of the adenoma. RESULTS: Parathyroidectomy was performed in 541 patients, 458 with PHPT and 83 with secondary hyperparathyroidism. In 345 of 380 patients (90.8%) with an adenoma, MIP was performed, and in 92 of these patients the operation was performed under local anesthesia. A total of 444 (97.0%) of the patients with PHPT were cured by the surgery. In 56 patients with a negative sestamibi scan, PTH-SVS was used preoperatively for localization of an adenoma. In 30 of these cases (53%) MIP was successfully performed in spite of a negative sestamibi scan. CONCLUSIONS: MIP is the treatment of choice for PHPT caused by a single adenoma. When the preoperative sestamibi scan is negative, the authors recommend the use of PTH-SVS for preoperative localization. This resulted in 53% successful MIP in patients with a negative sestamibi scan.

Diagnosing acute appendicitis in adults: accuracy of color Doppler sonography and MDCT compared with surgery and clinical follow-up.

OBJECTIVE: The objective of our study was to evaluate the accuracy of color Doppler sonography and contrast-enhanced MDCT in the diagnosis of acute appendicitis in adults and their utility as a triage tool in lower abdominal pain. MATERIALS AND METHODS: We reviewed the medical records of 420 consecutive adult patients, 271 women and 149 men, 18 years old or older, referred from the emergency department to sonography examination for clinically suspected acute appendicitis between January 2003 and June 2006. Patients underwent sonography of the right upper abdomen and pelvis followed by graded compression and color Doppler sonography of the right lower quadrant. CT was performed in 132 patients due to inconclusive sonography findings or a discrepancy between the clinical diagnosis and the sonography diagnosis. Sonography and CT reports were compared with surgery or clinical follow-up as the reference standard. Statistical analyses were performed by Pearson's chi-square test and cross-tabulation software. RESULTS: Sonography and CT correctly diagnosed acute appendicitis in 66 of 75 patients and in 38 of 39 patients, respectively, and correctly denied acute appendicitis in 312 of 326 and in 92 of 92 patients. Sonography was inconclusive in 17 of 418 cases and CT, in one of 132 cases. Sonography and CT allowed alternative diagnoses in 82 and 42 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for sonography were 74.2%, 97%, 88%, 93%, and 92%, respectively, and for CT, 100%, 98.9%, 97.4%, 100%, and 99%. CONCLUSION: Sonography should be the first imaging technique in adult patients for the diagnosis of acute appendicitis and triage of acute abdominal pain. CT should be used as a complementary study for selected cases.

Heparanase pretreatment attenuates endotoxin-induced acute lung injury in rats.

A central event of systemic inflammation and septic organ injury is infiltration of tissues with polymorphonuclear neutrophils, likely modulated by the integrity of the extracellular matrix underlying the vascular endothelium. In the present study, the effect of matrix-modifying endoglycosidase (heparanase) on endotoxin (LPS)-induced inflammatory lung injury was investigated in rats. Animals were treated with heparanase or LPS or pretreated with heparanase before LPS injection, and acute lung injury was verified histologically and characterized by analysis of bronchoalveolar lavage fluids. Pretreatment with heparanase attenuated the mortality of animals and preserved the histological structure of the lungs. Furthermore, polymorphonuclear neutrophil accumulation and activation, analyzed by myeloperoxidase release and reactive oxygen species production associated with lung injury, were significantly reduced upon heparanase pretreatment. In addition, heparanase pretreatment elevated the IL-10 levels in the pulmonary compartment. Moreover, results from in vitro experiments have identified monocyte-derived IL-10 as an important mediator used by heparanase to suppress inflammatory reactions. The protective effect of heparanase may indicate a novel therapeutic strategy for sepsis.

Use of the hemostatic agent QuikClot for the treatment of massive splenic injury in a rat model.

BACKGROUND: In the present study, QuikClot (QC) was used to treat intra-abdominal bleeding induced by massive splenic injury (MSI) in rats. STUDY DESIGN: 40 animals were divided into five groups: (1) sham operated; (2) MSI untreated; (3) MSI treated with 41.5 ml/kg lactated Ringer's solution (RL); (4) MSI treated with QC, and (5) MSI treated with QC and RL. RESULTS: Untreated MSI was followed by mortality of 60%, total blood loss (TBL) of 33.69% and mean survival time (MST) of 153.9 min. MSI treatment with RL resulted in mortality of 100%, TBL of 61.8% (p < 0.001), and MST of 92.2 min (p < 0.05). MSI treated with QC was followed by TBL of 14.1% (p < 0.005) and MST of 237.5 min (p < 0.05) with no mortality. MSI treated by QC and RL led TBL of 27.4% (p < 0.001 vs. group 3), and MST of 233.3 min (p < 0.05) and no mortality. CONCLUSIONS: QC significantly reduced blood loss from the injured spleen with improved survival. Combination of RL and QC prevented the increase in blood loss and improved survival compared to RL alone.

Adverse effects of increased intra-abdominal pressure on small bowel structure and bacterial translocation in the rat.

BACKGROUND: The purpose of this study was to evaluate the effects of elevated intra-abdominal pressure (IAP) on intestinal structures and bacterial translocation in the rat. MATERIALS AND METHODS: Forty-two male Sprague-Dawley rats were randomly divided into three experimental groups of 14 rats each: the sham group underwent insertion of a balloon-tipped catheter; the IAP-15 group was subjected to a 15 mm Hg pneumoperitoneum for 60 minutes; and the IAP-25 group was subjected to a 25 mm Hg pneumoperitoneum for 60 minutes. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) and bacterial translocation to mesenteric lymph nodes, liver, spleen, portal blood, and peripheral blood were determined 24 hours following pneumoperitoneum. RESULTS: IAP-15 and IAP-25 rats demonstrated a significant decrease in: bowel and mucosal weight in the duodenum, jejunum, and ileum; mucosal DNA and protein in the jejunum and ileum; villus height in the jejunum: and crypt depth in the jejunum and ileum compared to the sham rats. Bacterial translocation was demonstrated in 60% of IAP-15 rats and in 80% of IAP-25 rats. CONCLUSION: Elevated IAP results in mucosal injury of the gut, causing mucosal hypoplasia, and increases bacterial translocation.

The Impact of Age upon Contingency Planning for Multiple-casualty Incidents Based on a Single Center's Experience.

UNLABELLED: Introduction Trauma patients in the extremes of age may require a specialized approach during a multiple-casualty incident (MCI). Problem The aim of this study was to examine the type of injuries encountered in children and elderly patients and the implications of these injuries for treatment and organization. METHODS: A review of medical record files of patients admitted in MCIs in one Level II trauma center was conducted. Patients were classified according to age: children (≤12 years), adults (between 12-65 years), and elders (≥65 years). RESULTS: The files of 534 were screened: 31 (5.8%) children and 54 (10.1%) elderly patients. One-third of the elderly patients were either moderately or severely injured, compared to only 6.5% of the children and 11.1% of the adults (P<.001). Elderly patients required more blood transfusions (P=.0001), more computed tomography imaging (P=.0001), and underwent more surgery (P=.0004). Elders were hospitalized longer (P=.0003). There was no mortality among injured children, compared to nine (2.0%) of the adults and seven (13.0%) of the elderly patients (P<.0001). All the adult deaths occurred early and directly related to their injuries, whereas most of the deaths among the elderly patients (four out of seven) occurred late and were due to complications and multiple organ failure. CONCLUSIONS: Injury at an older age confers an increased risk of complications and death in victims of MCIs. Ashkenazi I , Einav S , Olsha O , Turegano-Fuentes F , Krausz MM , Alfici R . The impact of age upon contingency planning for multiple-casualty incidents based on a single center's experience. Prehosp Disaster Med. 2016;31(5):492-497.

Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: twenty years follow-up in 174 patients.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical procedure of choice for patients with ulcerative colitis and familial adenomatous polyposis. OBJECTIVES: To evaluate the long-term functional outcome of patients who underwent this surgical procedure. METHODS: We performed this observational study in 174 consecutive patients: 146 with UC and 28 with FAP. The patients, 91 males and 83 females with a mean age of 34.1+/-10.6 years (range 6-67 years), underwent the procedure between January 1984 and January 2004 (mean follow-up 64.8 months, range 1-240 months). The indications for surgery were intractable disease in 124 patients (71%), dysplasia in 36 (21%), severe bleeding in 8 (5%), and perforation in 6 (3%). RESULTS: A protective ileostomy was performed in 140 patients (96%) with UC and 12 (43%) with FAP. An urgent three-stage procedure was necessary in 14 patients (8.4%). A mucosal proctectomy was performed in 94 (54%), and a double stapling technique in 80 (46%). Mean length of hospital stay was 9.4+/-6.6 days (range 5-34 days, median 8). Complications included pelvic sepsis in 7 patients (4.2%), anastomotic leakage in 8 (4.8%), bowel obstruction in 22 (13.2%), incisional hernia in 12 (7.2%), anastomotic stenosis that usually responded to manual dilatation in 46 (27.6%), pouchitis in 106 (61%), recto-vaginal fistula in 3 (1.8%), retrograde ejaculation in 3 (1.8%), and impotence in 2 (1.2%). There was no mortality in this group of patients. The median number of bowel movements per 24 hours was six in UC patients and five in FAP patients, with at least one bowel movement during the night. Complete daytime and night-time continence was documented in 124 patients (71%). Overall satisfaction was 95%. CONCLUSIONS: Restorative proctocolectomy with ileal pouch-anal anastomosis confers a long-term good quality of life to both UC and FAP patients, and the majority of patients are fully continent with five to six bowel movements per day.

Transanal endoscopic microsurgery for rectal cancer.

BACKGROUND: Transanal endoscopic microsurgery has recently gained acceptance as an alternative minimally invasive surgical technique for the curative management of large rectal adenomas and selected early rectal carcinomas. OBJECTIVES: To analyze our 8 year experience using TEM for the management of rectal cancer. METHODS: Local resection by TEM was performed in patients with benign tumors and early rectal cancer. In addition, selected patients with T2 and T3 rectal cancers who were either medically unfit or unwilling to undergo radical surgery were also treated with this modality. Radical surgery was offered to all patients with incomplete tumor excision by TEM. RESULTS: Overall, 116 TEM operations for rectal tumors were carried out between 1995 and 2003, including 74 patients with rectal adenomas and 42 patients with rectal carcinomas. In 25 patients, TEM successfully removed all T1 tumors with clear tumor margins. Fourteen patients had T2 cancer and 3 of them (21%) required additional radical surgery due to incomplete excision. Local recurrence was observed in one patient with T2 cancer. There was no mortality. Major surgery or radiotherapy-related complications requiring additional surgical intervention was needed in five patients with T2 cancer. CONCLUSIONS: Local excision by TEM is a safe surgical procedure and should be offered to highly selected patients with early rectal cancer.

Minimally invasive surgery for treatment of hyperparathyroidism.

BACKGROUND: Minimal invasive surgery for parathyroidectomy has been introduced in the treatment of hyperparathyroidism. OBJECTIVE: To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy. METHODS: Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH measurements for intraoperative assessment. RESULTS: Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5, and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma. CONCLUSIONS: Preoperative localizationof the parathyroid gland by MIBI and ultrasound together with intraoperative iPTH measurements resulted in an overall cure rate of 98.6% for the entire series, The addition of ultrasound to the MIBI scan increased the accuracy of adenoma detection.

Maxillofacial and neck trauma: a damage control approach.

Severe maxillofacial and neck trauma exposes patients to life threatening complications such as airway compromise and hemorrhagic shock. These conditions require rapid actions (diagnosis and management) and a strong interplay between surgeons and anesthesiologists. Effective airway management often makes the difference between life and death in severe maxillofacial and neck trauma and takes initial precedence over all other clinical considerations. Damage control strategies focus on physiological and biochemical stabilization prior to the comprehensive anatomical and functional repair of all injuries. Damage control surgery (DCS) can be defined as the rapid initial control of hemorrhage and contamination, temporary wound closure, resuscitation to normal physiology in the intensive care unit (ICU) and subsequent reexploration and definitive repair following restoration of normal physiology. Damage control resuscitation (DCR) consists mainly of hypotensive (permissive hypotension) and hemostatic (minimal use of crystalloid fluids and utilization of blood and blood products) resuscitation. Both strategies should be administered simultaneously in all of these patients.

Improved survival in uncontrolled hemorrhagic shock induced by massive splenic injury in the proestrus phase of the reproductive cycle in the female rat.

Estrogen has a protective effect in adverse circulatory conditions such as trauma-hemorrhage and ischemia-reperfusion. In the present investigation uncontrolled hemorrhagic shock induced by massive splenic injury (MSI) was studied in male and female rats during the proestrus and metestrus phase of the reproductive cycle. The animals were anesthetized and randomly divided into four groups: group 1 (n = 8) were sham operated female animals; in group 2 (n = 8) MSI was induced in male animals; in group 3 (n = 8) MSI was induced in female animals in proestrus; in group 4 (n = 8) MSI was induced in female animals in metestrus. Plasma 17beta-estradiol was 112.8 +/- 16.7 pg/mL in group 3 and 44.8 +/- 16.7 pg/mL in group 4 (P < 0.04). After MSI the mean arterial pressure dropped in group 2 from 135.6 +/- 3.9 to 47.6 +/- 8.8 mmHg (P < 0.001) in 60 min. Total blood loss in 4 h was 29.6 +/- 3.5% of blood volume and mean survival time 161.3 +/- 30.6 min. In group 3 total blood loss in 4 h was 24.4 +/- 5.7% of blood volume and mean survival time 240 +/- 0 min (P < 0.03 compared with group 2). In group 4, total blood loss in 4 h was 29.6 +/- 3.9% of blood volume and mean survival time was 112.3 +/- 28.7 min (P < 0.001 compared with group 3). These results indicate that female rats in the proestrus phase of the reproductive cycle better maintain hemodynamic stability and survival in uncontrolled hemorrhagic shock than female animals in metestrus or males. This difference is attributed to factors other than blood loss.

Response of lung NK1.1-positive natural killer cells to experimental sepsis in mice.

Natural killer cells (NKC) participate in the initiation of the immune response and coordination between innate and adaptive immune mechanisms. Their role in systemic inflammation induced by trauma or infection (sepsis) is still controversial. In the present study, lung NKC and their response to experimental sepsis were investigated. Mice were subjected to cecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI). Animals were sacrificed 1, 4, and 7 days postoperatively, and lung histopathology, pulmonary vascular permeability, and inflammatory cells accumulation were assessed. On day 4, parameters of ALI were most prominent, and lung NK1.1+CD3- cells were isolated and studied by flow cytometry. Although CLP did not change the absolute number of lung NKC (2.47 +/- 0.52 x 10(5)/lung compared with 2.97 +/- 0.27 x 10(5)/lung in the sham group), the peak of the CLP-induced ALI was associated with severe dysfunction of lung NKC. Cell cytotoxicity decreased to 25.1 +/- 2.4% (P = 0.002), and percentage of perforin-positive NKC to 2.7 +/- 0.5% (P = 0.03). Cytokine profile of lung NK1.1+CD3- cells was prominently changed. The percentage of IFN-gamma-positive cells decreased to 19.7 +/- 5.7% (P = 0.047), but TNF-alpha-positive cells grew to 26.7 +/- 3.3% (P = 0.02). In summary, severe CLP-induced dysfunction of lung NK1.1+CD-3 cells was demonstrated. This may influence the outcome of the animals during sepsis and acute lung damage.

Divergent effects of oxygen therapy in four models of uncontrolled hemorrhagic shock.

Treatment with oxygen exerts beneficial effects and prolongs survival in hemorrhagic shock induced by controlled bleeding. We evaluated the effects of inhalation of 100% oxygen in four models of uncontrolled bleeding in rats: amputation of the tail, laceration of two branches of the ileocolic artery, incision of the spleen, and laceration of the lateral lobe of the liver. After tail amputation, oxygen caused a short and transient increase in mean arterial blood pressure (MABP; P < 0.01), decreased distal aorta (DA) blood flow by 27% (P < 0.01), and induced transient redistribution of blood flow to the superior mesenteric artery (SMA; P < 0.01). Later on, MABP in the oxygen group decreased gradually and was significantly lower than in air controls (P < 0.01). Oxygen therapy increased the mean blood loss by 40% (P < 0.01), increased blood lactate (P < 0.01), and shortened the survival time (P < 0.01). After laceration of two branches of the ileocolic artery, oxygen treatment caused a transient increase in MABP and redistribution of blood flow to the SMA that was followed by a comparable decrease in MABP, increase in vascular resistance, and decreased blood flow in the DA and SMA. In this model, oxygen did not affect bleeding volume, blood lactate, or survival. A similar transient regional hemodynamic effect was found when oxygen was administered after spleen or liver injury; however, in both models, oxygen maintained MABP at significantly higher values (P < 0.05). The results point to differential effects of oxygen in uncontrolled bleeding with benefits in bleeding from small parenchymal vessels and possible detrimental effect in bleeding from large size vessels.

Continuous fluid resuscitation for treatment of uncontrolled hemorrhagic shock following massive splenic injury in rats.

We have previously observed that bolus fluid resuscitation in uncontrolled hemorrhagic shock induced by solid organ injury leads to increased blood loss and mortality. In the present investigation, we studied the effect of continuous fluid resuscitation on the hemodynamic response and survival following massive splenic injury (MSI) in rats. The animals were randomized into 11 groups: group 1, sham-operated; group 2, MSI untreated; group 3, MSI treated with 17.5 mL/kg/h of Ringers lactate (RL) solution (RL-17.5); group 4, MSI treated with 35 mL/kg/h RL (RL-35); group 5, MSI treated with 70 mL/kg/h RL (RL-70); group 6, MSI treated with 7.5 mL/kg/h of 7.5% NaCl (HTS-7.5); group 7, MSI treated with 15 mL/kg/h of 7.5% NaCl (HTS-15); group S, MSI treated with 30 mL/kg/h of 7.5% NaCl (HTS-30); group 9, MSI treated with 7.5 mL/kg/h 6% hydroxyethyl starch (HES-7.5); group 10, MSI treated with 15 mL/kg/h 6% hydroxyethyl starch (HES-15); and group 11, MSI treated with 30 mL/kg/h 6% hydroxyethyl starch (HES-30). MSI in untreated group 2 was followed by a fall of mean arterial pressure (MAP) to 50.1 +/- 6.7 mmHg (P < 0.001) in 15 min. Mean survival time (MST) was 99.5 +/- 16.6 min, and total blood loss (TBL) was 37.8% +/- 2.6% of blood volume. Fluid treatment with increasing volumes of RL in groups 3, 4, and 5 was followed by a gradual increase in TBL compared with untreated animals, and MST remained unchanged. Increasing volumes of HTS infusion in groups 6, 7, and 8 was also followed by incease in TBL, but MST remained unchanged except for an increase to 123.0 +/- 20.5 min (P < 0.05) in group 6. Increasing volumes of HES in groups 9, 10, and 11 was also followed by increase in TBL, but MST remained unchanged. In conclusion, continuous infusion of LR, HTS, and HES following massive splenic injury resulted in a significant increase in intra-abdominal bleeding, but survival time in the first hour following injury remained unchanged in contrast to bolus fluid infusion, which increases early mortality.