Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases in murine renal carcinoma model.

The present studies were undertaken to evaluate the pulmonary pharmacokinetics and therapeutic efficacy of paclitaxel (PTX) administered by aerosol. PTX was encapsulated into dilauroylphosphatidylcholine liposomal formulations (PTX-DLPC). The deposition and clearance of PTX-DLPC in the lungs administered by aerosol or i.v. at comparative doses was performed, and PTX was quantitatively determined in tissue extracts by high-performance liquid chromatography analysis. The murine renal carcinoma (Renca) pulmonary metastases model was used to determine the therapeutic effect of drug formulation administered by aerosol. PTX-DLPC aerosols were generated with the Aero-Mist jet nebulizer (cis-USA). The most effective schedule of treatment was when mice inhaled the drug for 30 min 3 days per week. There was a significant reduction of the lung weights and reduced number of visible tumor foci on the lung surfaces of mice treated with PTX aerosol (P < 0.004 and P < 0.01, respectively) compared with control groups. Inhalation of PTX-DLPC also led to prolonged survival in mice inoculated with Renca cells. The results of the present studies demonstrate the therapeutic potential of aerosol technology for lung cancer treatment.

L-carnitine supplementation does not promote weight loss in ovariectomized rats despite endurance exercise.

In this five-week study, we tested the hypotheses that free access to a maintenance diet supplemented with L-carnitine (L-C) would reduce body fat in adult, sedentary, ovariectomized (OVX) rats, and that there would be an additive effect of L-C on weight reduction in swim-trained animals. As expected, serum carnitine was higher in rats fed the L-C diet, and the OVX-induced weight gain and abdominal fat were counteracted by swimming. L-C supplementation did not reduce the weight gain or abdominal fat in these adult female rats, Moreover, though not reaching statistical significance, rats that were fed L-C demonstrated a tendency for greater weight gain than their basal-fed counterparts despite no difference in energy intake. If the results of this study on ovariectomized rats can be translated to postmenopausal women, moderate intensity exercise may be recommended, but L-C supplementation, with no energy restriction, may be contraindicated as a weight loss method in this cohort.

Mediator-dependent secondary injury after unilateral blunt thoracic trauma.

The pathophysiologic sequence leading to respiratory failure after chest trauma can be an inevitable consequence of the primary injury or a secondary, mediator-driven inflammatory process. To distinguish between these alternatives, a simple cross-transfusion experiment was performed. A captive bolt gun injured the chest of anesthetized pigs that were mechanically ventilated with FiO2 = .21, .50, or .50 plus indomethacin (5 mg/kg intravenous; 15 min before injury). Tube thoracostomy immediately followed. After 30 min, blood from these injured donors was transfused into three matched groups of naive recipients (n = 8, 6, and 4, respectively) for a 33% exchange transfusion. Two control groups received blood from uninjured donors with tube thoracostomies only (FiO2 = .21, n = 7; FiO2 = .50, n = 10). Within 15-30 min after transfusion, in recipients from injured donors versus controls, lung compliance was decreased 20%, stroke volume and cardiac output were decreased 50%, and pulmonary vascular resistance was increased >300% (all p < .05). These changes recovered to baseline within 60-90 min. The stable metabolite of thromboxane A2, thromboxane B2, increased >500% in plasma within 15 min and remained elevated for >120 min. All responses were similar at 21 % or 50% O2, which suggests that hypoxia per se is not a cause of mediator production. All responses were eliminated by indomethacin. By 24 h, histologic changes included atelectasis in 3/3 recipients from injured donors versus 0/3 recipients from uninjured donors. We conclude that 1) blunt chest trauma releases blood borne mediators, including prostanoids; 2) these mediators can cause secondary cardiopulmonary changes in naive recipients similar to those produced by chest trauma; 3) the progression to trauma-induced respiratory failure is multifactorial; 4) early pharmacologic intervention, rather than supportive care alone, may benefit some victims of severe chest trauma.

Reduction of vancomycin-resistant enterococcal infections by limitation of broad-spectrum cephalosporin use in a trauma and burn intensive care unit.

Both vancomycin and third-generation cephalosporin use are believed to contribute to a rise in vancomycin-resistant enterococci (VRE) infections. In 1998, the largest number of VRE infections in our hospital occurred in the trauma/burn intensive care unit (TBICU), accounting for nearly 20% of hospital infections. In an attempt to control the VRE infection rate, antibiotic protocols for prophylaxis, empiric, and definitive therapy were initiated during the final quarter of 1998 to minimize cephalosporin use by the introduction of piperacillin/tazobactam. Therefore, we undertook a study of the VRE infection rate for the TBICU in relation to vancomycin, piperacillin/tazobactam, piperacillin, third-generation cephalosporin, and total cephalosporin use before and after efforts to limit cephalosporins. These data were compared to those in the medical and surgical intensive care units. During 1998, seven VRE infections occurred in the TBICU. Following initiation of antibiotic protocols, one case of VRE infection occurred in the subsequent month and no cases in the 17 months since. The decrease in the VRE infection rate corresponded with a significant increase in the use of piperacillin/tazobactam and a reduction in third-generation and total cephalosporin use. In contrast, cephalosporin use in the medical and surgical intensive care units remains significantly higher than in the TBICU, and neither unit has had a reduction in their VRE infection rates.

Recurrent trauma in elderly patients.

HYPOTHESIS: Older patients (those aged > or = 70 years) who have experienced trauma have an increased risk of recurrent trauma. Demographic, medical, and functional factors are potential contributors to the risk of subsequent trauma among injured elderly patients. DESIGN: Retrospective follow-up study. PARTICIPANTS: Study participants were derived from the Longitudinal Study of Aging, an extension of the 1984 National Health Interview Survey focusing on persons who were aged 70 years and older in 1984. A cohort of elderly patients participating in the Longitudinal Study of Aging and hospitalized for injury in 1985 (n = 100) was identified using Medicare hospital discharge data. An uninjured cohort (n = 401) was also identified from the Longitudinal Study of Aging and matched for age (1 year) and sex. MAIN OUTCOME MEASURES: Risk of admission for trauma among the injured cohort compared with the uninjured cohort and associations between demographic, medical, and functional characteristics and trauma recurrence. RESULTS: Following adjustment for potential confounding factors, the injured cohort was 3.25 times more likely (95% confidence interval, 1.99-5.31) to be hospitalized for injury during the follow-up period compared with the uninjured cohort. Among the injured cohort, those at greatest risk of subsequent trauma included women and those with chronic medical conditions or functional impairments, the latter being the only factor independently associated with recurrence. CONCLUSIONS: Elderly patients who have experienced trauma are at increased risk of subsequent injury. Interventions to reduce the likelihood of trauma recurrence should focus on those with chronic illnesses and functional impairments.

Some biomechanical considerations of polytetrafluoroethylene sutures.

The biomechanical performance of polytetrafluoroethylene (PTFE) sutures has been compared with that of polypropylene sutures, the standard to which other sutures used in vascular and cardiac surgery are compared. The PTFE is supple and has no plastic memory, while the polypropylene suture is stiff and retains its plastic memory. In addition, the rate of creep encountered in the PTFE suture was significantly less than that of the polypropylene suture. The knotting profiles for knot security for either a square, granny, or surgeon's knot for polypropylene sutures were three throws each. In contrast, knot security with either a square or granny PTFE knot was accomplished with seven throws; six throws were needed for a secure surgeon's knot. The breaking strength of the unknotted and knotted PTFE sutures was approximately one half as great as that for the unknotted and knotted polypropylene sutures. Knot construction significantly reduced the breaking strength of polypropylene sutures but did not alter the breaking strength of PTFE sutures. The percent elongation experienced by both sutures before breakage did not differ significantly. The elasticity, as measured by work recovery, for the polypropylene suture was greater than that for the PTFE suture. On the basis of its unique biomechanical performance characteristics, the PTFE suture should have an important place in vascular and cardiac surgery.

Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries.

BACKGROUND: Although early enteral feeding clearly reduces septic morbidity after blunt and penetrating trauma, data for head-injured patients are conflicting. This study examines the effects of early vs delayed enteral feedings on outcome in patients with severe closed-head injuries with a Glasgow Coma Scale (GCS) score greater than 3 and less than 11. METHODS: Thirty patients were prospectively randomized to receive an immune-enhancing diet (Impact with fiber) early (initiated < 72 hours after trauma) delivered via an endoscopically placed nasoenteric tube (Stay-Put) or late (administered after gastric ileus resolved). This formula was continued for 14 days or until the patient tolerated oral feeding. Goal rate of nutrition was 21 nonprotein cal/kg/d and 0.3 g N/kg/d. RESULTS: Two patients in the early group were excluded due to inability to place the tube, and one patient in the late group died before 72 hours. Five of the remaining 27 died, 1 in the early group and 4 in the late group. There were no significant differences between the groups in length of stay, intensive care unit (ICU) days, significant infection, or GCS score. However, major infection correlated inversely with admission GCS score (R = -0.6, p < .003). Time to reach a GCS score of 14 was significantly longer in patients with significant infections compared with those without (p < .02). CONCLUSIONS: No difference in length of stay or infectious complications is shown in patients with severe closed-head injury when they are given early vs delayed feeding using an immune-enhancing formula. Severity of the head injury is closely associated with significant infection.

Prognostic factors in patients with inferior vena cava injuries.

Inferior vena cava (IVC) injuries are potentially devastating insults that continue to be associated with high mortality despite advances in prehospital and in-hospital critical care. Between 1987 and 1996, 37 patients (32 males and 5 females; average age, 30 years) were identified from the trauma registry as having sustained IVC trauma. Overall mortality was 51 per cent (n = 19), with 13 intraoperative deaths and five patients dying within the first 48 hours. Blunt IVC injuries (n = 8) had a higher associated mortality than penetrating wounds (63% versus 48%). Of the 29 patients with penetrating IVC trauma, the wounding agent influenced mortality (shotgun-100% versus gunshot-43% versus stab-0%). Anatomical location of injury was also predictive of death [suprahepatic (n = 3)-100% versus retrohepatic (n = 9)-78% versus suprarenal (n = 6)-33% versus juxtarenal (n = 2)-50% versus infrarenal (n = 15)-33%]. A direct relationship existed between outcome and the number of associated injuries: nonsurvivors averaged four and survivors averaged three. Eighty per cent of patients sustaining four or more associated injuries died, by contrast to a 33 per cent mortality in those suffering less than four injuries. Physiological factors were also predictive of outcome. Patients in shock (systolic blood pressure < 80) on arrival had a higher mortality than those who were hemodynamically stable (76% versus 30%). Preoperative lactate levels were of prognostic value for death (> or = 4.0-59% versus < 4.0-0%), as was base deficit (< 4-22%, > or = 4, and < 10-36%, > or = 10-73%). Interestingly, neither time from injury to hospital arrival (47.4 minutes versus 33.0 minutes) nor time in the emergency department before surgery (45.6 minutes versus 42.6 minutes) differed between survivors and fatalities. Mortality remained high in the 34 patients who had operative control of their IVC injuries [lateral repair (n = 27)-44% versus ligation (n = 6)-66% versus Gortex graft (n = 1)-0%]. As wounding agent, anatomical location, associated injuries, and physiological status seem to most directly impact mortality, future efforts must focus both on establishing prevention programs directed at reducing the incidence of this injury, as well as on advancing the management of those who do survive to hospitalization, if we are to improve on the outcome of these devastating injuries.

Trauma-specific intensive care units can be cost effective and contribute to reduced hospital length of stay.

Our hypothesis was that clinical outcomes are improved and cost and hospital length of stay (LOS) reduced as a result of the opening of a closed trauma intensive care unit (ICU). We conducted a cross-sectional study in a university-affiliated Level I trauma center. Our study population comprised trauma patients admitted to the ICU between June 1, 1996 and July 1, 1998 for at least 24 hours and with an Injury Severity Score (ISS) >16 (excluding those with severe brain injury). The main outcome measures were changes in LOS and number of ventilator days, prevalence of complications, changes in patient charges, and hospital costs. Two hundred four patients were included [trauma ICU (TICU) 60, surgical ICU 144]. The two groups were not statistically different in age, ISS, mechanism of injury, infection rate, and mortality; however, the TICU patients had a lower number of ventilator hours (83.1 vs 100.0; P = 0.007), lower ICU LOS (9.4 vs 12.1 days; P = 0.06), and lower total hospital LOS (15.6 vs 22.3 days; P = 0.01). Although this was not of statistical significance TICU patients had lower hospital charges ($125,383 vs $152,994; P = 0.06) and lower cost per case ($42,306 vs $47,548; P = 0.35) for a net savings of $314,520 during the first 6 months of operation of the TICU. This study suggests that improved clinical outcomes and decreases in cost and LOS are directly related to the opening of a closed trauma ICU.

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.

The effects of n-3 fatty acid supplementation on bleeding time, plasma fatty acid composition, and in vitro platelet aggregation in cats.

Dietary supplementation with fish and fish oils rich in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to alter eicosanoid metabolism and impair platelet function in several species. As an initial step in evaluating the antithrombotic effect of these n-3 fatty acids in cats, purified EPA and DHA were administered daily to 8 clinically normal cats for 2 months. Platelet function was evaluated biweekly by determining mucosal bleeding time and in vitro platelet aggregation parameters. Plasma fatty acid profiles were obtained before fish oil supplementation and at the termination of the study. In spite of significant increases (P < .0001) in the plasma concentrations of EPA and DHA after n-3 fatty acid supplementation, there were no significant changes in platelet aggregation or bleeding times. Although it is tempting, based on extrapolation of data from other species, to recommend dietary supplementation with fish oil for cats prone to arterial thromboembolism, these results indicate that administration of large doses of purified EPA and DHA once daily does not inhibit platelet function in normal cats and is unlikely to prevent thrombosis in cats with cardiovascular disease. Additional studies are recommended to ascertain whether more frequent administration of these purified n-3 fatty acids or continual feeding of diets high in n-3 fatty acid content will impair platelet function.

Effects of feeds on flavor of red meat: a review.

The effects of diet ingredients on red meat flavor are dependent on the type of diet, and, to a large extent, on the species: pork, mutton or lamb and beef. Sensory analysis of meat flavor has been used in most of the studies on the effects of feeds on meat flavor. In general, high-energy grain diets produced a more acceptable or a more intense flavor in red meats than low-energy forage or grass diets. Feeding pigs unsaturated fats increases the unsaturation in pork fat but results in only minor changes in pork flavor. Sheep must be fed protected, unsaturated fats in order to increase the unsaturation in their fat to be similar to pork fat. This increased unsaturation results in a greater flavor change in lamb or beef than in pork. Several dietary ingredients such as fish products, raw soybeans, canola oil and meal, and pasture grasses cause undesirable flavors in red meat. Analyses of lamb and beef produced on different diets have shown that type of feed affects the concentration of many flavor volatile compounds. However, only a few studies have quantified the volatiles of beef and lamb produced on different diets, and no reports of studies were found in which the volatiles of pork produced on different diets had been investigated. Hence, the importance of these changes in volatile concentration to meat flavor has not been determined.

Feeding encapsulated ground full-fat soybeans to increase polyunsaturated fat concentrations and effects on flavor volatiles in fresh lamb.

This research assessed the potential of increasing PUFA concentrations and the effect on flavor volatiles in red meat by feeding ground, full-fat soybean supplemented in casein complex. Supplements consisted of untreated ground, full-fat soybean (CO) or ground, full-fat soybeans treated with acetaldehyde (AC) or diacetyl (DA) to form gels. On a DM basis, the control (CO), AC, and DA supplements contained 48.6, 50.0, and 49.1% CP and 17.3, 17.3, and 17.4% fat, respectively. Weaned feeder lambs (n = 18) were divided into three treatment groups with two pens of three lambs per group. One of three supplements (200 g of DM) plus 1 kg DM of a ground corn basal diet and 0.36 kg DM of grass hay was fed daily to each of six lambs in a group for 9 wk. Samples of the intramuscular (LM), intermuscular, subcutaneous, and kidney fat were obtained from each lamb carcass for determination of total lipid contents and fatty acid profiles. Flavor volatiles of broiled LM were also analyzed. Total fat content of the LM was 3.7, 4.6, and 2.6% for lambs consuming diets supplemented with CO, AC, and DA, respectively. Compared with lambs fed the untreated supplement (CO), lambs supplemented with AC or DA had 1) higher (P < 0.05) concentrations of linoleic (4.80 vs. 6.37 or 6.80%) and linolenic (0.28 vs. 0.43 or 0.45%) acids in the LM nonpolar lipids; 2) a higher (P < 0.05) concentration of linoleic acid (22.1 vs. 27.1 or 25.6%), but a lower (P < 0.05) concentration of oleic acid (17.2 vs. 13.0 or 13.1%), in the LM polar lipids; 3) a higher (P < 0.05) concentration of linoleic acid (3.77 vs. 6.13 or 6.06%) in subcutaneous fat; and 4) higher (P < 0.05) concentrations of linoleic (4.46 vs. 7.65 or 7.13%), linolenic (0.50 vs. 0.85 or 0.80%), and stearic (24.9 vs. 27.2 or 26.9%) acids, but a lower (P < 0.05) concentration of oleic acid (39.1 vs. 35.4 or 36.3%), in kidney fat. In broiled LM chops, 21 volatiles were identified, including seven alkanals, seven 2-alkenals, two 2,4-alkadienals, and five other compounds, but most differences in the volatile concentrations among lambs fed the different supplements did not correspond to concentration differences in their precursor fatty acids. Results indicated that compared with the untreated supplement (CO), AC and DA supplements protected linoleic (C 18:2n6) and linolenic (C18:3n3) acids in soybean oil from degradation in the rumen of the lambs, resulting in increased deposition in the muscle and adipose tissues of lamb.

Vacuum-assisted complex wound closure with elastic vessel loop augmentation: a novel technique.

Patients with serious abdominal or soft-tissue injuries may require multistaged surgical management. The Vacuum-Assisted Closure device, used in combination with a shoelace technique, can promote fascial and soft-tissue approximation.

Where's the tube? Evaluation of hand-held ultrasound in confirming endotracheal tube placement.

INTRODUCTION: The diagnosis of endotracheal tube (ETT) mal-position may be delayed in extreme environments. Several methods are utilized to confirm proper ETT placement, but these methods can be unreliable or unavailable in certain settings. Thoracic sonography, previously utilized to detect pneumothoraces, has not been tested to assess ETT placement. HYPOTHESIS: Thoracic sonography could correlate with pulmonary ventilation, and thereby, help to confirm proper ETT placement. METHODS: Thirteen patients requiring elective intubation under general anesthesia, and data from two trauma patients were evaluated. Using a portable, hand-held, ultrasound (PHHU) machine, sonographic recordings of the chest wall visceral-parietal pleural interface (VPPI) were recorded bilaterally in each patient during all phases of airway management: (1) pre-oxygenation; (2) induction; (3) paralysis; (4) intubation; and (5) ventilation. RESULTS: The VPPI could be well-imaged for all of the patients. In the two trauma patients, right mainstem intubations were noted in which specific pleural signals were not seen in the left chest wall VPPI after tube placement. These signs returned after correct repositioning of the ETT tube. In all of the elective surgery patients, signs correlating with bilateral ventilation in each patient were imaged and correlated with confirmation of ETT placement by anesthesiology. CONCLUSIONS: This report raises the possibility that thoracic sonography may be another tool that could be used to confirm proper ETT placement. This technique may have merit in extreme environments, such as in remote, pre-hospital settings or during aerospace medical transports, in which auscultation is impossible due to noise, or capnography is not available, and thus, requires further scientific evaluation.

Surgical instrument restraint in weightlessness.

BACKGROUND: Performing a surgical procedure during spaceflight will become more likely in the future as the duration of missions becomes longer. Only minimal surgical capability was available on previous missions since the definitive medical care time was short and the likelihood of a surgical event too low to justify carrying surgical hardware onboard. Early demonstrations of surgical procedures in the microgravity environment of parabolic flight indicated the need for careful logistical planning and restraint of surgical hardware. Human ergonomics also has more effect in microgravity than in the conventional 1-G environment. METHODS: Three methods of surgical instrument restraint--a Minor Surgical Kit (MSK), a Surgical Restraint Scrub Suit (SRSS), and a Surgical Tray (ST)--were evaluated in parabolic flight surgical procedures. RESULTS: The MSK was easily stored, easily deployed, and demonstrated the best ability to facilitate a surgical procedure in microgravity. CONCLUSION: Important factors in a surgical restraint system for microgravity include excellent organization of supplies, ability to maintain sterility, accessibility while providing secure restraint, ability to dispose of sharp items and biological trash, and ergonomic efficiency.

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.

Classic selective sweeps were rare in recent human evolution.

Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of "classic selective sweeps" (in which a beneficial mutation arises and rapidly fixes in the population).Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past ~250,000 years.