Lower body negative pressure reduces jugular and portal vein volumes and counteracts the elevation of middle cerebral vein velocity during long-duration spaceflight.

Cephalad fluid shifts in space have been hypothesized to cause the spaceflight-associated neuro-ocular syndrome (SANS) by increasing the intracranial-ocular translaminal pressure gradient. Lower body negative pressure (LBNP) can be used to shift upper-body blood and other fluids toward the legs during spaceflight. We hypothesized that microgravity would increase jugular vein volume (JVvol), portal vein cross-sectional area (PV), and intracranial venous blood velocity (MCV) and that LBNP application would return these variables toward preflight levels. Data were collected from 14 subjects (11 males) before and during long-duration International Space Station (ISS) spaceflights. Ultrasound measures of JVvol, PV, and MCV were acquired while seated and supine before flight and early during spaceflight at day 45 (FD45) and late at day 150 (FD150) with and without LBNP. JVvol increased from preflight supine and seated postures (46 ± 48% and 646 ± 595% on FD45 and 43 ± 43% and 702 ± 631% on FD150, P < 0.05), MCV increased from preflight supine (44 ± 31% on FD45 and 115 ± 116% on FD150, P < 0.05), and PV increased from preflight supine and seated (51 ± 56% on FD45 and 100 ± 74% on FD150, P < 0.05). Inflight LBNP of -25 mmHg restored JVvol and MCV to preflight supine level and PV to preflight seated level. Elevated JVvol confirms the sustained neck-head blood engorgement inflight, whereas increased PV area supports the fluid shift at the splanchnic level. Also, MCV increased potentially due to reduced lumen diameter. LBNP, returning variables to preflight levels, may be an effective countermeasure.NEW & NOTEWORTHY Microgravity-induced fluid shifts markedly enlarge jugular and portal veins and increase cerebral vein velocity. These findings demonstrate a marked flow engorgement at neck and splanchnic levels and may suggest compression of the cerebral veins by the brain tissue in space. LBNP (-25 mmHg for 30 min) returns these changes to preflight levels and, thus, reduces the associated flow and tissue disturbances.

Growth inhibitory and apoptosis-inducing effects of xanthohumol, a prenylated chalone present in hops, in human prostate cancer cells.

Promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of hormone-refractory prostate cancer. Xanthohumol (XN), a prenylated chalcone-derived from hops, has shown strong antitumorigenic activity towards diverse types of cancer cells. In the present study, the growth-inhibitory and apoptosis-inducing activity of XN was tested in hormone-sensitive and hormone-refractory human prostate cancer cells lines. Cell growth/viability assay (MTS) demonstrated that prostate cancer cells are highly sensitive to XN at a concentration range of 20-40 µM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of annexin V-FITC, cleavage of PARP-1, activation of procaspases -3, -8, and -9, mitochondrial depolarization and release of cytochrome c from mitochondria. Induction of apoptosis by XN was associated with the inhibition of prosurvival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2 and survivin. These studies provide a rationale for clinical evaluation of XN for the treatment of hormone-refractory metastatic prostate cancer.

Diagnostic ultrasound at MACH 20: retroperitoneal and pelvic imaging in space.

An operationally available diagnostic imaging capability augments spaceflight medical support by facilitating the diagnosis, monitoring and treatment of medical or surgical conditions, by improving medical outcomes and, thereby, by lowering medical mission impacts and the probability of crew evacuation due to medical causes. Microgravity-related physiological changes occurring during spaceflight can affect the genitourinary system and potentially cause conditions such as urinary retention or nephrolithiasis for which ultrasonography (U/S) would be a useful diagnostic tool. This study describes the first genitourinary ultrasound examination conducted in space, and evaluates image quality, frame rate, resolution requirements, real-time remote guidance of nonphysician crew medical officers and evaluation of on-orbit tools that can augment image acquisition. A nonphysician crew medical officer (CMO) astronaut, with minimal training in U/S, performed a self-examination of the genitourinary system onboard the International Space Station, using a Philips/ATL Model HDI-5000 ultrasound imaging unit located in the International Space Station Human Research Facility. The CMO was remotely guided by voice commands from experienced, earth-based sonographers stationed in Mission Control Center in Houston. The crewmember, with guidance, was able to acquire all of the target images. Real-time and still U/S images received at Mission Control Center in Houston were of sufficient quality for the images to be diagnostic for multiple potential genitourinary applications. Microgravity-based ultrasound imaging can provide diagnostic quality images of the retroperitoneum and pelvis, offering improved diagnosis and treatment for onboard medical contingencies. Successful completion of complex sonographic examinations can be obtained even with minimally trained nonphysician ultrasound operators, with the assistance of ground-based real-time guidance.

Snowboarding injuries: a review of the literature and an analysis of the potential use of portable ultrasound for mountainside diagnostics.

Snowboarding has become a popular recreational and professional sport. Participants suffer a variety of injuries, especially of the extremities, that require medical evaluation. This article reviews the reported injuries to both leisure and elite athletes. To many, an injured extremity requires travel to a medical facility for accurate evaluation. Musculoskeletal ultrasound is an accurate and portable technology that can be used for real time, mountainside diagnoses of these injuries.

Hand-held thoracic sonography for detecting post-traumatic pneumothoraces: the Extended Focused Assessment with Sonography for Trauma (EFAST).

BACKGROUND: Thoracic ultrasound (EFAST) has shown promise in inferring the presence of post-traumatic pneumothoraces (PTXs) and may have a particular value in identifying occult pneumothoraces (OPTXs) missed by the AP supine chest radiograph (CXR). However, the diagnostic utility of hand-held US has not been previously evaluated in this role. METHODS: Thoracic US examinations were performed during the initial resuscitation of injured patients at a provincial trauma referral center. A high frequency linear transducer and a 2.4 kg US attached to a video-recorder were used. Real-time EFAST examinations for PTXs were blindly compared with the subsequent results of CXRs, a composite standard (CXR, chest and abdominal CT scans, clinical course, and invasive interventions), and a CT gold standard (CT only). Charts were reviewed for in-hospital outcomes and follow-up. RESULTS: There were 225 eligible patients (207 blunt, 18 penetrating); 17 were excluded from the US examination because of battery failure or a lost probe. Sixty-five (65) PTXs were detected in 52 patients (22% of patients), 41 (63%) being occult to CXR in 33 patients (14.2% whole population, 24.6% of those with a CT). The US and CXR agreed in 186 (89.4%) of patients, EFAST was better in 16 (7.7%), and CXR better in 6 (2.9%). Compared with the composite standard, the sensitivity of EFAST was 58.9% with a likelihood ratio of a positive test (LR+) of 69.7 and a specificity of 99.1%. Comparing EFAST directly to CXR, by looking at each of 266 lung fields with the benefit of the CT gold standard, the EFAST showed higher sensitivity over CXR (48.8% versus 20.9%). Both exams had a very high specificity (99.6% and 98.7%), and very predictive LR+ (46.7 and 36.3). CONCLUSION: EFAST has comparable specificity to CXR but is more sensitive for the detection of OPTXs after trauma. Positive EFAST findings should be addressed either clinically or with CT depending on hemodynamic stability. CT should be used if detection of all PTXs is desired.

Percutaneous aspiration of fluid for management of peritonitis in space.

BACKGROUND: As a medical emergency that can affect even well-screened, healthy individuals, peritonitis developing during a long-duration space exploration mission may dictate deviation from traditional clinical practice due to the absence of otherwise indicated surgical capabilities. Medical management can treat many intra-abdominal processes, but treatment failures are inevitable. In these circumstances, percutaneous aspiration under sonographic guidance could provide a "rescue" strategy. HYPOTHESIS: Sonographically guided percutaneous aspiration of intra-peritoneal fluid can be performed in microgravity. METHODS: Investigations were conducted in the microgravity environment of NASA's KC-135 research aircraft (0 G). The subjects were anesthetized female Yorkshire pigs weighing 50 kg. The procedures were rehearsed in a terrestrial animal lab (1 G). Colored saline (500 mL) was introduced through an intra-peritoneal catheter during flight. A high-definition ultrasound system (HDI-5000, ATL, Bothell, WA) was used to guide a 16-gauge needle into the peritoneal cavity to aspirate fluid. RESULTS: Intra-peritoneal fluid collections were easily identified, distinct from surrounding viscera, and on occasion became more obvious during weightless conditions. Subjectively, with adequate restraint of the subject and operators, the procedure was no more demanding than during the 1-G rehearsals. CONCLUSIONS: Sonographically guided percutaneous aspiration of intra-peritoneal fluid collections is feasible in weightlessness. Treatment of intra-abdominal inflammatory conditions in spaceflight might rely on pharmacological options, backed by sonographically guided percutaneous aspiration for the "rescue" of treatment failures. While this risk mitigation strategy cannot guarantee success, it may be the most practical option given severe resource limitations.

In-vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects.

Biolistic transmission of mRNA provides transient gene therapy to in vivo organs. This study documents particle mediated mRNA transmission to a solid organ and wound healing model using the mRNA of Green Fluorescent Protein to determine optimal delivery parameters. Renal function, bullet penetration, cellular injury, and Green Fluorescent Protein synthesis were quantified. Chimeric human epidermal growth factor-FLAG epitope cDNA or mRNA was transmitted to wounds in normal or steroid treated animals. Wound bursting strength, human epidermal growth factor-FLAG, and collagen synthesis were determined. Injury and bullet penetration correlated with the delivery velocity and bullet size. Optimal delivery parameters were established which provided widespread Green Fluorescent Protein synthesis. Human epidermal growth factor-FLAG treatment significantly increased collagen content and wound breaking strength in normal and steroid treated animals. FLAG protein synthesis was evident in mRNA treated fascia following treatment. We found the gene gun provides a novel method for efficient, in vivo delivery of mRNA-based therapeutic strategies to mammalian organs with minimal histologic damage allowing transient expression of protein in in vivo target tissues. Co-delivery of Green Fluorescent Protein mRNA may provide a useful positive control to determine effective transmission. Biolistic transmission of human epidermal growth factor-FLAG mRNA provides increased tissue epidermal growth factor levels and accelerates wound healing in normal and steroid exposed animals.

Ultrasound evaluation of the magnitude of pneumothorax: a new concept.

Pneumothorax is commonly seen in trauma patients; the diagnosis is confirmed by radiography. The use of ultrasound where radiographic capabilities are absent, is being investigated by the National Aeronautics and Space Administration. We investigated the ability of ultrasound to assess the magnitude of pneumothorax in a porcine model. Sonography was performed on anesthetized pigs in both ground-based laboratory (n = 5) and microgravity conditions (0 x g) aboard the KC-135 aircraft during parabolic flight (n = 4). Aliquots of air (50-100 cm3) were introduced into the chest to simulate pneumothorax. Results were videorecorded and digitized for later interpretation. Several distinct sonographic patterns of partial lung sliding were noted including the combination of a sliding zone with a still zone and a "segmented" sliding zone. These "partial lung sliding" patterns exclude massive pneumothorax manifested by a complete separation of the lung from the parietal pleura. In 0 x g, the sonographic picture is more diverse; one x g differences between posterior and anterior aspects are diminished. Modest pneumothorax can be inferred by the ultrasound sign of "partial lung sliding." This finding, which increases the negative predictive value of thoracic ultrasound, may be attributed to intermittent pleural contact, small air spaces, or alterations in pleural lubricant. Further studies of these phenomena are warranted.

Prospective evaluation of thoracic ultrasound in the detection of pneumothorax.

BACKGROUND: Thoracic ultrasound may rapidly diagnose pneumothorax when radiographs are unobtainable; the accuracy is not known. METHODS: We prospectively evaluated thoracic ultrasound detection of pneumothorax in patients at high suspicion of pneumothorax. The presence of "lung sliding" or "comet tail" artifacts were determined in patients by ultrasound before radiologic verification of pneumothorax by residents instructed in thoracic ultrasound. Results were compared with standard radiography. RESULTS: There were 382 patients enrolled; the cause of injury was blunt (281 of 382), gunshot wound (22 of 382), stab wound (61 of 382), and spontaneous (18 of 382). Pneumothorax was demonstrated on chest radiograph in 39 patients and confirmed by ultrasound in 37 of 39 patients (95% sensitivity); two pneumothoraces could not be diagnosed because of subcutaneous air; the true-negative rate was 100%. CONCLUSION: Thoracic ultrasound reliably diagnoses pneumothorax. Expansion of the focused abdominal sonography for trauma (FAST) examination to include the thorax should be investigated for terrestrial and space medical applications.

Endoscopic surgery in weightlessness: the investigation of basic principles for surgery in space.

BACKGROUND: Performing a surgical procedure in weightlessness, also called 0-gravity (0-g), has been shown to be no more difficult than in a 1-g environment if the requirements for the restraint of the patient, operator, surgical hardware, are observed. The performance of laparoscopic and thorascopic procedures in weightlessness, if feasible, would offer several advantages over the performance of an open operation. Concerns about the feasibility of performing minimally invasive procedures in weightlessness have included impaired visualization from the absence of gravitational retraction of the bowel (laparoscopy) or thoracic organs (thoracoscopy) as well as obstruction and interference from floating debris such as blood, pus, and irrigation fluid. The purpose of this study was to determine the feasibility of performing laparoscopic and thorascopic procedures and the degree of impaired surgical endoscopic visualization in weightlessness. METHODS: From 1993 to 2000, laparoscopic and thorascopic procedures were performed on 10 anesthetized adult pigs weighing approximately 50 kg in the National Aeronautics and Space Administration (NASA) Microgravity Program using a modified KC-135 airplane. The parabolic simulation system for advanced life support was used in this project, and 20 to 40 parabolas were used for laparoscopic or thorascopic investigation, each containing approximately 30 s of 0-g alternating with 2-g pullouts. The animal model was restrained in the supine position on a floor-level Crew Medical Restraint System, and the abdominal cavity was insufflated with carbon dioxide. The intraabdominal and intrathoracic anatomy was visualized in the 1-g, 0-g, and 2-g periods of parabolic flight. Bleeding was created in the animals, and the behavior of the blood in the abdominal and thoracic cavities was observed. In the thoracic cavity, gas insufflation and mechanical retraction was used at times unilaterally to decrease pulmonary ventilation enough to increase the thoracic domain. RESULTS: Visualization was improved in laparoscopy, from tethering of the bowel by the elastic mesentery, and from the strong tendency for debris and blood to adhere to the abdominal wall because of surface tension forces. The lack of adequate thoracic domain made thorascopy more difficult. Fluid in the thoracic cavity did not impair visualization because the fluid at 0-g does not loculate posteriorly, but disperses along the thoracic wall and mediastinal reflections. CONCLUSIONS: Performing minimally invasive procedures instead of open surgical procedures in a weightless environment has theoretical advantages, especially in the ability to prevent cabin atmosphere contamination from surgical fluids (blood, pus, irrigation). Visualization will become more important and practical as the endoscopic hardware is miniaturized from its current form, as endoscopic technology becomes more advanced, and as more surgically capable medical crew officers are present in future long-duration space exploration missions.

Effect of acute hemodilution on intestinal perfusion and intramucosal pH after shock.

BACKGROUND: Restoration of oxygen delivery, especially to the splanchnic bed, is of critical importance during trauma resuscitation. Acute normovolemic hemodilution (ANH) has been used to reduce blood transfusion requirement during elective surgery. The effect of hemodilution on the splanchnic circulation during hemorrhagic shock (HS) is not well defined. METHODS: Swine were instrumented to measure systemic and splanchnic circulation effects of ANH after HS. The adequacy of the splanchnic circulation was assessed by changes in measured mucosal blood flow, mucosal tonometry, as well as by portal venous blood O2 saturation, portal venous CO2 saturation, and lactate. RESULTS: ANH after HS resulted in a final hematocrit of 18+/-2%. Superior mesenteric artery blood flow was returned to baseline levels; however, mucosal blood flow was still only 64% of baseline levels. However, at the same time mucosal PCO2 and intramucosal pH as well as portal venous O2 and CO2 saturation had normalized. CONCLUSION: As long as an adequate intravascular volume is maintained, hemodilution is well tolerated by the gut after HS. Concern about the adequacy of gut perfusion should not be a transfusion trigger after HS.

Detection of surgical glove integrity.

Surgical glove integrity is essential for universal precautions; glove safety is verified by the water load test (WLT). Concerns regarding glove injury have prompted newer testing methodologies, including electrical conductance testing (ECT); however, the sensitivities of these tests are not known. We compared the sensitivity of WLT and ECT in detecting glove needle-stick injury in two commonly used brands of surgical gloves. Punctures were made with hollow-bore and solid surgical needles of various configurations. The WLT failed to detect glove holes from the smallest-caliber needles and only detected the injury in 60 per cent for the largest caliber. The ECT provided a graded index of glove injury in all holes made by both solid surgical needles and hollow-bore needles. The WLT is a poor test for clinical defects in latex surgical gloves; the ECT is significantly more sensitive and provides a gauge of the cross-sectional area of the defect. Interbrand differences in self-sealing properties of surgical gloves were evidenced and may be clinically relevant after glove perforation.

Synergistic effects of Candida and Escherichia coli on gut barrier function.

BACKGROUND: Disruption of the indigenous gut microflora with overgrowth of gram-negative bacteria and Candida species is common in the critically ill patient. These organisms readily translocate in vitro, which may cause septic complications and organ failure. A synergistic effect between Escherichia coli and C. albicans in polymicrobial infections has been demonstrated. An interaction between these organisms at the mucosal barrier is unknown. METHODS: Ca(CO2) monolayers were grown to confluence in a two compartment culture system. E. coli and C. albicans or E. coli alone were added to the apical chambers. Secretory immunoglobulin A was added to half of the apical chambers as well. Cell cultures were incubated for a total of 240 minutes. Basal media were sampled at timed intervals for quantitative culture. Monolayer integrity was confirmed by serial measurement of transepithelial electrical resistance. RESULTS: Secretory immunoglobulin A decreased bacterial translocation across Ca(CO2) monolayers challenged with E. coli alone. Transepithelial passage of E. coli was significantly increased by coculture of bacteria with C. albicans. Augmentation of bacterial translocation by Candida occurred even in the presence of secretory immunoglobulin A. CONCLUSIONS: Candida colonization of the GI tract may impair mucosal barrier defense against gram-negative bacteria. The clinical role of gut antifungal prophylaxis in protecting against gut derived gram-negative sepsis is speculative.

Hemorrhagic shock impairs mucosal immunity to gut-derived antigens.

Secretory immunoglobulin A (sIgA) is the principal antibody protecting against pathogens in the respiratory tract and other mucosal surfaces. Nosocomial pneumonias are frequent after injury and critical illness and are often due to enteric pathogens. The aim of this study was to assess the relative effect of hemorrhagic shock (HS) on mucosal immunity at intestinal and respiratory mucosal sites. Fisher rats were immunized intragastrically with dinitrophenylated (DNP) Pneumococcus (Pn). Three weeks later, animals were subjected to sham treatment or HS. The animals were then rechallenged with DNP-Pn 1 or 3 days later. Animals were sacrificed 7 days later, and bronchoalveolar and gastric lavage was performed. Total and anti-DNP-specific sIgA were quantitated from these secretions by enzyme-linked immunosorbent assay. There was a significant decrease in DNP-Pn-specific sIgA at 72 hours after HS, which was not present in animals at 24 hours after HS. This was most profound in bronchoalveolar lavage specimens. We conclude that impaired mucosal defense against gut-derived antigens after HS may be important mechanistically for the development of posttraumatic pneumonia and other mucosally related infectious complications.

Impact of trauma stress ulcer prophylaxis guidelines on drug cost and frequency of major gastrointestinal bleeding.

Trauma patients are routinely prescribed stress ulcer prophylaxis despite evidence suggesting such therapy be limited to patients with identifiable risk factors for bleeding. With surgeons' consensus, we developed and implemented trauma stress ulcer prophylaxis guidelines, and measured the impact of clinical pharmacists on implementing the guidelines and the effect of the guidelines on drug cost and frequency of major gastrointestinal bleeding. Two groups of 150 consecutive patients admitted with multiple trauma were evaluated before and after guideline implementation and stratified by Injury Severity Score (ISS) to minor (ISS < 9) or moderate to severe (ISS > or = 9) trauma groups. The number of patients prescribed stress ulcer prophylaxis, length and cost of this therapy, and number of patients experiencing major gastrointestinal bleeding (decrease in consecutive hemoglobin > or = 2 g/dl in conjunction with coffee-ground emesis, hematemesis, melena, or hematochezia) were measured. All pharmacist interventions pertaining to stress prophylaxis were collected. Fewer patients were prescribed stress ulcer prophylaxis after guideline implementation (105/150, 70% vs 39/150, 26%, p<0.0001), leading to a decrease in total drug cost of $4558. Use decreased more in patients with minor (40/54, 74% vs 9/59, 15%, p<0.0001) than moderate to severe (65/96, 68% vs 30/91, 33%, p<0.0001) trauma. Neither length of therapy nor agent of choice (> 95% cimetidine) differed between groups. Fifteen (38%) of 38 postguideline prophylaxis orders were determined by the pharmacist not to meet guideline criteria. Recommendations to discontinue therapy were accepted in 9 (60%) of 15 instances. The frequency of major gastrointestinal bleeding remained unchanged between groups (1/150 vs 0/150, p=1.0). Implementation of trauma stress ulcer prophylaxis guidelines limiting therapy to patients with risk factors for bleeding led to a 80% decrease in drug cost and did not affect the frequency of major gastrointestinal bleeding.

Synergistic effect of hyperoxia and immunoglobulin A on mucosal barrier defense.

BACKGROUND: Hyperoxia has been reported to be protective against gut-derived sepsis. Although secretory immunoglobulin A (IgA) is primarily responsible for humoral defense of mucosal surfaces, a potential synergistic effect with hyperoxia is unknown. An asanguineous cell monolayer system was used to study these aspects in vitro. METHODS: MDCK cells were grown as polarized monolayers in a two-chamber culture system. Apical chambers were inoculated with 10(8) Escherichia coli M14 with or without polyclonal IgA and incubated in a 21 or 95% O2 environment. Basal medium was sampled at 90 and 180 minutes for bacterial translocation. In a second experiment, MDCK cells were lysed at 90 minutes and intracellular bacteria were quantitated. RESULTS: Bacterial translocation was decreased versus normoxia by the treatment groups IgA without hyperoxia or IgA with hyperoxia at 90 minutes. Bacterial internalization at 90 minutes was reduced to the greatest extent by the combined effects of hyperoxia and IgA. Translocation data at 180 minutes confirmed the additional protective effect of hyperoxia with IgA. CONCLUSION: Hyperoxia exerts a significant protective effect on barrier function independent of enhanced leukocyte function. Hyperoxia has an added effect to the mucosal defense provided by IgA.

Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock.

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.