Impact of Different Positive End-Expiratory Pressures on Lung Mechanics in the Setting of Moderately Elevated Intra-Abdominal Pressure and Acute Lung Injury in a Porcine Model.

The effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics in acute respiratory distress syndrome (ARDS) have still not been fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP and ARDS is unclear. In this paper, 18 pigs under general anesthesia received a double hit lung injury. After saline lung lavage and 2 h of injurious mechanical ventilation to induce an acute lung injury (ALI), an intra-abdominal balloon was filled until an IAP of 10 mmHg was generated. Animals were randomly assigned to one of three groups (group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH2O) and ventilated for 6 h. We measured end-expiratory lung volume (EELV) per kg bodyweight, driving pressure (ΔP), transpulmonary pressure (ΔPL), static lung compliance (Cstat), oxygenation (P/F ratio) and cardiac index (CI). In group A, we found increases in ΔP (22 ± 1 vs. 28 ± 2 cmH2O; p = 0.006) and ΔPL (16 ± 1 vs. 22 ± 2 cmH2O; p = 0.007), with no change in EELV/kg (15 ± 1 vs. 14 ± 1 mL/kg) when comparing hours 0 and 6. In group B, there was no change in ΔP (26 ± 2 vs. 25 ± 2 cmH2O), ΔPL (19 ± 2 vs. 18 ± 2 cmH2O), Cstat (21 ± 3 vs. 21 ± 2 cmH2O/mL) or EELV/kg (12 ± 2 vs. 13 ± 3 mL/kg). ΔP and ΔPL were significantly lower after 6 h when comparing between group C and A (21 ± 1 vs. 28 ± 2 cmH2O; p = 0.020) and (14 ± 1 vs. 22 ± 2 cmH2O; p = 0.013)). The EELV/kg increased over time in group C (13 ± 1 vs. 19 ± 2 mL/kg; p = 0.034). The P/F ratio increased in all groups over time. CI decreased in groups B and C. The global lung injury score did not significantly differ between groups (A: 0.25 ± 0.05, B: 0.21 ± 0.02, C: 0.22 ± 0.03). In this model of ALI, elevated IAP, ΔP and ΔPL increased further over time in the group with a PEEP of 5 cmH2O applied over 6 h. This was not the case in the groups with a PEEP of 10 and 15 cmH2O. Although ΔP and ΔPL were significantly lower after 6 hours in group C compared to group A, we could not show significant differences in histological lung injury score.

Effect of moderate elevated intra-abdominal pressure on lung mechanics and histological lung injury at different positive end-expiratory pressures.

INTRODUCTION: Intra-abdominal hypertension (IAH) is a well-known phenomenon in critically ill patients. Effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics are still not fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP is unclear. METHODS: We investigated changes in lung mechanics and transformation in histological lung patterns using three different PEEP levels in eighteen deeply anesthetized pigs with an IAP of 10 mmHg. After establishing the intra-abdominal pressure, we randomized the animals into 3 groups. Each of n = 6 (Group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH2O). End-expiratory lung volume (EELV/kg body weight (bw)), pulmonary compliance (Cstat), driving pressure (ΔP) and transpulmonary pressure (ΔPL) were measured for 6 hours. Additionally, the histological lung injury score was calculated. RESULTS: Comparing hours 0 and 6 in group A, there was a decrease of EELV/kg (27±2 vs. 16±1 ml/kg; p<0.05) and of Cstat (42±2 vs. 27±1 ml/cmH2O; p<0.05) and an increase of ΔP (11±0 vs. 17±1 cmH2O; p<0.05) and ΔPL (6±0 vs. 10±1 cmH2O; p<0.05). In group B, there was no significant change in EELV/kg (27±3 vs. 24±3 ml/kg), but a decrease in Cstat (42±3 vs. 32±1 ml/cmH20; p<0.05) and an increase in ΔP (11±1 vs. 15±1 cmH2O; p<0.05) and ΔPL (5±1 vs. 7±0 cmH2O; p<0.05). In group C, there were no significant changes in EELV/kg (27±2 vs. 29±3 ml/kg), ΔP (10±1 vs. 12±1 cmH2O) and ΔPL (5±1 vs. 7±1 cmH2O), but a significant decrease of Cstat (43±1 vs. 37±1 ml/cmH2O; p<0.05). Histological lung injury score was lowest in group B. CONCLUSIONS: A moderate elevated IAP of 10 mmHg leads to relevant changes in lung mechanics during mechanical ventilation. In our study, a PEEP of 10 cmH2O was associated with a lower lung injury score and was able to overcome the IAP induced alterations of EELV.

Circadian rhythm and day to day variability of serum potassium concentration: a pilot study.

BACKGROUND: Hyperkalemia is a common and life-threatening complication frequently seen in patients with acute kidney injury, end-stage renal disease and chronic heart failure. Cardiac arrest and ventricular fibrillation are possible consequences. Biosensors are currently being developed to measure serum potassium under ambulatory conditions and trigger an alarm if the potassium concentration exceeds normal limits. Only few studies exist on the circadian rhythm of potassium; and its dependence on age and kidney function is less clear. METHODS: Our observational monocentric exploratory study included 30 subjects of which 15 had impaired renal function (RF) (GFR <60 ml/min/1.73 m(2)). Subjects were further categorized into three age groups: 18-39 years (N normal RF = 5, N impaired RF = 4), 40-59 years (N normal RF = 5, N impaired RF = 6), 60-80 years (N normal RF = 5, N impaired RF = 5). Serum potassium levels were measured every 2 h during a 24 h period and repeated once after 2, 4, or 6 days. RESULTS: In the 15 subjects with normal RF, the lowest mean potassium level (3.96 ± 0.14 mmol/l) was observed at 9 p.m. and the greatest (4.23 ± 0.23 mmol/l) at 1 p.m. In patients with impaired RF the lowest mean potassium level (4.20 ± 0.32 mmol/l) was observed at 9 p.m. and the highest (4.57 ± 0.46 mmol/l) at 3 p.m. The range between the mean of minimum and maximum was greater in patients with impaired RF (0.71 ± 0.45 mmol/l) than in subjects with normal RF (0.53 ± 0.14 mmol/l) [p < 0.001]. No difference in the circadian rhythm was found between the first and second examination. CONCLUSION: Our results indicate that patients with normal and impaired RF have comparable circadian patterns of serum potassium concentrations, but higher fluctuations in patients with impaired RF. These results have clinical relevance for developing an automatic biosensor to measure the potassium concentration in blood under ambulatory conditions in patients at high risk for potassium fluctuations.

Creation and detection of Skyrmions in a Bose-Einstein condensate.

We present the first experimental realization and characterization of two-dimensional Skyrmions and half-Skyrmions in a spin-2 Bose-Einstein condensate. The continuous rotation of the local spin of the Skyrmion through an angle of pi (and half-Skyrmion through an angle of pi/2) across the cloud is confirmed by the spatial distribution of the three spin states as parametrized by the bending angle of the l vector. The winding number w = (0,1,2) of the internal spin states comprising the Skyrmions is confirmed through matter-wave interference.

Near-field amplitude and phase recovery using phase-shifting interferometry.

Scattering-type scanning near-field optical microscopy has allowed for investigation of light-matter interaction of a large variety of samples with excellent spatial resolution. Light incident on a metallic probe experiences an amplitude and phase change on scattering, which is dependent on optical sample properties. We implement phase-shifting interferometry to extract amplitude and phase information from an interferometric near-field scattering system, and compare recorded optical images with theoretical predictions. The results demonstrate our ability to measure, with nanoscale resolution, amplitude and phase distributions of optical fields on sample surfaces. The here-introduced phase-shifting method is considerably simpler than heterodyne methods and less sensitive to errors than the two-step homodyne method.

Cysteinyl-tRNA synthetase is not essential for viability of the archaeon Methanococcus maripaludis.

The methanogenic archaea Methanocaldococcus jannaschii and Methanothermobacter thermautotrophicus contain a dual-specificity prolyl-tRNA synthetase (ProCysRS) that accurately forms both prolyl-tRNA (Pro-tRNA) and cysteinyl-tRNA (Cys-tRNA) suitable for in vivo translation. This intriguing enzyme may even perform its dual role in organisms that possess a canonical single-specificity cysteinyl-tRNA synthetase (CysRS), raising the question as to whether this latter aminoacyl-tRNA synthetase is indeed required for cell viability. To test the postulate that all synthetase genes are essential, we disrupted the cysS gene (encoding CysRS) of Methanococcus maripaludis. The knockout strain was viable under normal growth conditions. Biochemical analysis showed that the pure M. maripaludis ProCysRS was capable of forming Cys-tRNA, implying that the dual-specificity enzyme compensates in vivo for the loss of CysRS. The canonical CysRS has a higher affinity for cysteine than ProCysRS, a reason why M. maripaludis may have acquired cysS by a late lateral gene transfer. These data challenge the notion that all twenty aminoacyl-tRNA synthetases are essential for the viability of a cell.

Secondary healing of Mohs defects of the forehead, temple, and lower eyelid.

OBJECTIVE: To analyze the results of secondary healing of Mohs defects of the forehead, temple, and lower eyelid. DESIGN: Scars resulting from secondary healing in these 3 sites were rated by patient interviews and by analysis of postoperative photographs by 3 board-certified members of the American Academy of Facial Plastic and Reconstructive Surgery. SETTING: Private facial plastic and reconstructive surgery practice in Florida. PATIENTS: Patients with Mohs wounds of the forehead, temple, and lower eyelid that were allowed to heal by secondary intention between January 1, 1989, and December 31, 1993, who were available for follow-up. There were 10 wounds of the forehead, 6 of the temple, and 10 of the lower eyelid that were available for analysis. MAIN OUTCOME MEASURES: Wound color, contour, distortion of surrounding structures, presence of telangiectasias or paresthesias, pain or infection during healing, and overall cosmetic result. RESULTS: Color, contour, and overall scar cosmesis were rated using the following scale: poor (0), fair (1), good (2), and excellent (3). Telangiectasias, paresthesias, and pain or infection during healing were recorded as present or absent. The respective color and contour ratings for the 3 sites were 2.2 and 2.2 for the forehead, 2.5 and 2.7 for the temple, and 2.7 and 3 for the lower eyelid according to patient interview and 1 and 1.3 for the forehead, 1 and 1.4 for the temple, and 2.6 and 2.5 for the lower eyelid according to surgeon analysis. Pain, infection, paresthesias, and distortion of surrounding structures were rare, but 7 of 10 forehead and 4 of 6 temple wounds had telangiectasias. CONCLUSIONS: Many defects of the forehead and temple will heal with acceptable results. Partial-thickness or small full-thickness lower eyelid wounds heal with excellent cosmetic and functional results. Patient satisfaction is greater than might be predicted by surgeon analysis of wound healing.

Refusal of treatment, leading to death: towards optimization of informed consent.

Few medical decisions create more anguish than ones involving cessation of treatment, resulting in the death of a patient. In this article, the ethical and legal aspects of the withdrawal of treatment are examined with respect to a case of a 67-year-old man who fell and sustained a fracture of his second cervical vertebra, rendering him paralysed and respirator-dependent. He immediately requested the withdrawal of treatment, but his family baulked. Ethics consultation recommended delaying the decision, to give the patient enough time to foster optimal comprehension and synthesis of information related to his condition and the consequences; we refer to this process as "optimization of informed consent." When the patient was informed of the delay and the reasons for it, he was assured (and subsequently repeatedly reassured) of his ultimate right to refuse treatment at a future date. On balance, optimization of informed consent promotes patients' autonomy, even though it involves suspending this autonomy for a time. It is also consistent with physicians' responsibility to promote life and avoid premature death.

Sinonasal undifferentiated carcinoma: a ray of hope.

In 1987, we published a case series of a newly-described, highly malignant neoplasm, termed sinonasal undifferentiated carcinoma, in which treatment results were poor. In this updated study, we report the followup for the original three surviving patients and for six additional cases whose tumors were diagnosed between January 1987 and October 1991. These data suggest that the prognosis for patients with localized disease may be better than originally described.

Hemodynamic considerations in organ and tissue patterning of B16 melanoma systemic metastasis and colonization.

Several populations of the mouse B16 melanoma that are highly metastatic from subcutaneous transplants but differ in growth characteristics were compared with regard to systemic site patterning of visible metastasis, as well as colonization effected by intracardiac injection of tumor cells. In all cases, metastasis proceeded in two stages, initially to the lungs and secondarily from lung metastases to systemic sites. The relative ranking of systemic site involvement by secondary-stage metastasis was basically similar for all tumor cell populations; the overall hierarchy was: kidneys greater than brain greater than adrenals and ovaries greater than pancreas greater than mesentery. Colonization patterns resulting from intracardiac injection were also generally comparable but differed from metastasis patterning in that the kidneys and brain were poorly colonized while the bones were frequent sites of colonization. Enumeration of fluoresceinated tumor cells or microbeads trapped in various sites following intracardiac injection revealed a ranking of initial involvement that differed markedly from colony formation. These results indicate that the hemodynamics of blood flow is not a critical determinant of colonization patterning. Based on the colonizing behavior of microbead-bound tumor cells, the frequent metastatic involvement of the kidneys and brain appears to result from selective trapping of large multicell tumor emboli within arteries in those organs. The occurrence of metastasis in other systemic sites is, like colonization, not readily explained by hemodynamics.

NMR spectroscopy evaluation of plasma "oncolipids" in head and neck cancer.

The use of water-suppressed proton nuclear magnetic resonance spectroscopy of plasma as a serologic test for the detection of malignancy was first described in 1986. That report prompted the present study, which was undertaken to evaluate the efficacy of this test in differentiating patients who have head and neck malignancy from normal controls. Forty-six patients who had a biopsy-proven malignancy of the head and neck and 32 healthy individuals provided plasma for which the nuclear magnetic resonance spectrum was plotted, blind to patient diagnosis or group. The average line-width of methyl and methylene resonance was calculated. Significant differences (p less than 0.05) were found between the group with disease and the group with no disease for the methyl line-widths, using analysis of variance. In spite of this statistical difference, plotting of the values for the methyl, methylene, and average line-widths clearly demonstrated that these three oncolipid measures have no clinical use because of the tremendous overlap between the disease and nondisease groups. The findings of this study do not support the use of water-suppressed proton nuclear magnetic resonance spectroscopy as a clinically useful test for the diagnosis of head and neck malignancy.

Clinicopathologic features of cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

The clinicopathologic features of 32 cutaneous squamous cell carcinomas of the head and neck in 12 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were examined to determine the frequency of clinically aggressive and histologically poorly differentiated carcinomas in this group of patients. Two thirds of the neoplasms were multiple and 56% were high grade (grade 3 or 4). One of the 12 patients had recurrent carcinoma, two patients had recurrent and metastatic disease, and two patients had metastatic tumor without recurrence. Two patients died of tumor, one patient is alive with extensive recurrent and metastatic disease, and one patient died of an uncertain type of carcinoma. An additional patient with squamous cell carcinoma of the face died of cutaneous squamous cell carcinoma that arose on the chest. This study shows that cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma are often high grade and have the potential for recurrence and metastasis.

Radiotelemetric assessment of grid-trapping techniques in a study of the eastern chipmunk (Tamias striatus L.).

Grid trapping has been used to determine small mammal home ranges for almost 50 years. In the absence of a more precise standard against which to calibrate, at least nine trap data interpretation methods have been developed, each yielding different values. Home ranges generated from these methods were compared to those calculated using much more accurate radio telemetry to determine the former's relative precisions. The standard circle and Koeppl's 70% ellipse generated home ranges closest to those determined with radiotelemetry. Assumptions concerning the accuracy of peripheral successful traps in defining boundaries of home ranges were tested, as were those concerning spatial utilization near unsuccessful traps within the home range.