The decay of 133mXe.

The decay of (133m)Xe has been re-measured using an electron-transporter spectrometer and a planar HPGe detector. The sample of (133m)Xe was produced by means of proton-induced fission using an ion-guide based on-line mass separator. The deduced K and L+M+... shell conversion coefficients, alpha(Kappa)=6.5(9) and alpha(L+M+...)=2.9(4), agree within the uncertainty limits with the theoretical values and remove the inconsistencies between the previous experimental studies of (133m)Xe.

Design of an air sampler for a small unmanned aerial vehicle.

In the aftermath of a nuclear accident or malevolent act, it is of paramount importance to have the capability to monitor airborne radioactive substances by collecting air samples. For potentially dangerous missions, the Radiation and Nuclear Safety Authority of Finland (STUK) has developed an air sampler to be used on a small unmanned aerial vehicle. When a Petrianov or Fluoropore filter is used in the sampler and the air velocity is 71 km h(-1), the air flow rate through the filter is 0.73 m(3) h(-1) or 0.23 m(3) h(-1), respectively. The present article introduces the developed air sampler using fluid dynamic simulations and wind tunnel data. The operation of the system was validated by collecting airborne radioactive aerosols from air.

An empirical comparison of case-control and trio based study designs in high throughput association mapping.

Motivated by high throughput genotyping technology, our aim in this study was to experimentally compare the power and accuracy of case-control and family trio based approaches for haplotype based, large scale, association gene mapping. We compared trio based and case-control study designs in different disease models, and partitioned the performance differences into separate components: those from the sample ascertainment, the effective sample size, and the haplotyping approaches. For systematic and controlled tests, we simulated a rapidly expanding and relatively young isolated population. The experiments were also replicated with real asthma data. We used computationally efficient methods that scale up to large amounts of both markers and individuals. Mapping is based on a haplotype association test for haplotypes of 1-10 markers. For population based haplotype reconstruction, we use HaploRec, and compare it to both a simple trio based inference and true haplotypes. Firstly and surprisingly, statistically inferred population based haplotypes can be equally powerful as true haplotypes. Secondly, as expected, the effective sample size has a clear effect on both gene detection power and mapping accuracy. Thirdly, the sample ascertainment method does not have much effect on mapping accuracy. Finally, an interesting side result is that the simple haplotype association test clearly outperformed exhaustive allelic transmission disequilibrium tests. The results suggest that the case-control design is a powerful alternative to the more laborious family based ascertainment approach, especially for large datasets, and wherever population stratification can be controlled.

Cell kinetic analysis of a murine macrophage cell line.

For the present study, which was performed to find a reliable method suitable for determination of the cell kinetic parameters of a continuous cell line, use was made of the macrophage cell line J774.1. The doubling time of the cell population was approximately 27 h. The continuous labeling curve showed that all the cells divide and almost no quiescent cells occur. The cell-cycle time as determined from the curve of the labeled cells in mitosis, the course of the stathmokinetic index, and time-lapse videorecordings, was about 19 h. The discrepancy between the population doubling time and the cell-cycle time must be due to death and disintegration of cells during culture in vitro. The results indicate that the doubling time of a cell population is not a reliable parameter to determine the kinetics of a population of continuously proliferating cells and that determination of the course of the stathmokinetic index offers a rapid and simple method to establish the cell-cycle time reliably.

Chalones: concepts and results.

Control of cell proliferation is executed, in part, by means of negative feedback, utilizing cell-line specific messenger substances called chalones. Although knowledge of chalone chemistry is still in its infancy, the reality of the concept can no longer be reasonably questioned. In particular, it has recently been shown that chalones are even capable of causing tumour regression both in animals and in man. In addition to overviewing the chalone concept, we show here that the chalone-induced tumour regression is readily explained in simple and plausible terms.

Abnormal in vivo response to sodium nitroprusside after porcine single lung transplantation.

The chronic increase of pulmonary vascular resistance after lung transplantation is only partly due to an active increase in baseline vasomotor tone, but the nature of the acute pulmonary hypertension after ischemia and reperfusion is not known. We studied the effects of sodium nitroprusside on pulmonary hemodynamics during reperfusion in porcine left lung allotransplants. In twelve pigs (weight: 18 to 24 kg) pulmonary arteries of the native and the transplanted lung were cannulated for right-heart bypass. The total blood flow was 2 L/min. Flow distribution between the lungs was measured at equal mean pulmonary artery pressure, and pulmonary vascular resistance at equal and constant flow-i.e., 1 L/min to each lung. After baseline measurements sodium nitroprusside (1, 3, and 9 microg/kg/min) was administered to six animals (SNP group). The control group (n=6) received an equal amount of the vehicle. After 30 min of discontinuation of the drug infusion, the schedule was repeated. In the transplanted lung, pulmonary vascular resistance decreased in all animals during the first hour of reperfusion. During the second drug infusion pulmonary vascular resistance was significantly lower in the SNP group compared with the control group only at the highest infusion rate of the drug (9 microg/kg/min), which also induced a 44% decrease in systemic vascular resistance. Arterial oxygen tension remained comparable in the two groups throughout the study. Our data suggest that other factors besides active vasoconstriction may contribute to the acute increase of pulmonary vascular resistance after lung transplantation.

Pulmonary inactivation of 5-hydroxytryptamine is decreased during cigarette smoke ventilation of rat isolated lungs.

1 The effect of cigarette smoke ventilation on the inactivation of [14C]-5-hydroxytryptamine (5-HT) was studied in isolated perfused lungs of the rat. 2 [14C]-5-HT 9.6 nmol was infused into the pulmonary circulation of rat lungs in 3 min. The nonrecirculating perfusion effluent was collected during the 5-HT infusion in three consecutive 1 min fractions. The amount of metabolites of 5-HT was determined from the perfusion effluent and from the perfused lungs. 3 The amount of metabolites of 5-HT in the perfused lungs was also decreased by cigarette smoke ventilation, although the total amount of radioactivity in the lung tissue was not significantly changed. 5 The decreased pulmonary inactivation of 5-HT may cause increased circulating levels of 5-HT, which would explain some cardiovascular changes during smoking.

Effects of cigarette smoke on the metabolism of vasoactive hormones in rat isolated lungs.

1. The effects of exposure of rats to cigarette smoke have been studied on the metabolism of vasoactive hormones in isolated lungs from these animals. 2. Rats were exposed for 1 h per day to cigarette smoke for 1 day or for 10 days. 3. Angiotensin I conversion was increased after 1 day's exposure but after 10 days' exposure conversion returned to normal. 4. Inactivation of prostaglandin E2 was decreased after 1 day's exposure. After 10 days' exposure there was a further decrease which could not be attributed to smoke alone. 5. The inactivation of 5-hydroxytryptamine and bradykinin remained unchanged after both short and longer exposures to smoke. 6. The metabolic activity of the lung towards some vasoactive hormones in the pulmonary circulation is affected by exposure of the animal to cigarette smoke and such changes may be relevant to the initiation of cardiovascular changes consequent upon cigarette smoking.

Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting.

Oxygen free radicals mediate the ischemia-reperfusion damage in animal hearts, but their role in human beings is still controversial because of the low xanthine oxidase level in the human heart. Besides ischemia-reperfusion, cardiac operation also includes other major interventions that might generate free radicals but have not been systematically studied. We studied the cases of nine patients throughout coronary artery operations, including general anesthesia, heparin, protamine and administration of cardioplegic solution, extracorporeal circulation, and heart reperfusion. Arterial plasma was assayed for malondialdehyde, diene conjugates, and fluorescent chromolipids, and plasma antioxidant activity was estimated from the ability to trap peroxyl radicals. Anesthesia, surgical procedures, or heparin administration did not change these parameters. Extracorporeal circulation decreased the plasma concentration of diene conjugates immediately, whereas other compounds remained unaltered. When these concentrations were corrected for hemodilution, the amount of fluorescent chromolipids actually increased after 5 minutes of extracorporeal circulation to 177% +/- 14% (mean +/- standard error of the mean), diene conjugates increased to 138% +/- 12%, and plasma antioxidant capacity increased to 144% +/- 12% of the awake value. Fluorescent chromolipid values remained at 156% to 177% throughout the perfusion and decreased to 130% +/- 13% 1 hour after perfusion. Diene conjugate levels and antioxidant capacity were 123% to 144% and 143% to 161%, respectively, from baseline during perfusion and 119% +/- 5% and 135% +/- 9%, respectively, 1 hour after perfusion. Heart reperfusion or protamine administration showed no additional increases. Malondialdehyde concentrations varied and showed no statistically significant alterations. We conclude that extracorporeal circulation devices induce generation of free radicals and plasma antioxidant activity, which are different from the damage caused by ischemia-reperfusion.

Pulmonary vasodilatory properties of prostaglandin E1 are blunted after experimental single lung transplantation.

BACKGROUND: Pulmonary dysfunction and right heart failure are still a common clinical problem after single lung transplantation. METHODS: In this study we investigated the pulmonary vasodilatory properties of prostaglandin E1 in pigs during the first 4 hours after left lung allotransplantation. With the use of extracorporeal circulation and total right heart bypass, the right and left pulmonary arteries could be individually perfused and the drug effect in each lung separately analyzed either at equal blood pressures or at equal blood flows in the pulmonary arteries. Twelve animals received in a randomized double-blind fashion either saline solution or an increasing prostaglandin E1 infusion (10, 25, 50, and 100 ng/kg/min; 15 minutes each). After a drug-free period of 75 minutes, the infusion schedule with 25, 50, and 100 ng/kg/min was repeated. RESULTS: During the first part of the study the highest dose of prostaglandin E1 decreased the mean systemic arterial pressure by 25%, but an almost similar decrease occurred in the control animals. During the second infusion period a 28% decrease was observed only in the animals treated with prostaglandin E1. None of the infusions was able to decrease pulmonary vascular resistance. Instead prostaglandin E1 diverted two thirds of the pulmonary blood flow toward the native lung, and this diversion manifested itself as an earlier improvement of the arterial oxygen tension in the drug-treated animals. The end-tidal carbon dioxide values measured from each lung corresponded to those from the common expiratory limb of the system, but there was a distinct gradient in the range of 14 to 20 mm Hg between the arterial and end-tidal carbon dioxide values. CONCLUSIONS: We conclude that prostaglandin E1, in doses tolerated by the systemic circulation, is ineffective in the treatment of the increased pulmonary vascular resistance after single lung transplantation.

Thromboxane receptor blockade does not attenuate pulmonary pressor response in porcine single lung transplantation.

BACKGROUND: The ischemia-reperfusion lung injury is characterized by increased pulmonary vascular resistance, edema, and subsequent deterioration of oxygenation. Other models of acute lung injury suggest that thromboxane A2 may contribute to the pulmonary hypertension after transplantation. METHODS: We studied the effects of the selective thromboxane A2 receptor antagonist SQ 30741 on pulmonary hemodynamics and gas exchange in porcine single lung transplantation using extracorporeal circulation (right heart bypass) with separate cannulations of the right and left pulmonary arteries. Pulmonary vascular resistance was measured at equal and constant flow to each lung. Flow distribution between the lungs was registered at equal pulmonary artery pressures. Twelve pigs (weight 17 to 23 kg) were studied. At the onset of reperfusion a bolus dose of the drug (5 mg/kg) was injected into both pulmonary arteries followed by an infusion (5 mg/kg/hr) for 1 hour (SQ group, n = 6). The control group (n = 6) received an equal amount of vehicle. The systemic and pulmonary hemodynamics and blood gas values were registered during 2 hours of reperfusion. RESULTS: The pulmonary vascular resistance of the transplanted lung was significantly higher compared with the native lung (p < 0.001). Administration of SQ 30741 failed to ameliorate the pulmonary pressor response of the graft in comparison with the control group. No difference was found in the systemic arterial oxygen tension between the two groups. CONCLUSIONS: Thromboxane does not seem to be among the principal mediators in the pulmonary hypertension after transplantation.

L-Arginine in lung graft preservation and reperfusion.

BACKGROUND: Inhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion. METHODS: Six pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue. RESULTS: Pulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine. CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Effects of acid-base imbalance on pulmonary angiotensin-converting enzyme in vivo.

The effects of acid-base balance disturbances on pulmonary endothelial angiotensin-converting enzyme (ACE) were studied in anesthetized mechanically ventilated rabbits. Enzyme function was estimated from [3H]benzoyl-Phe-Ala-Pro ([3H]BPAP) utilization under first-order reaction conditions during a single transpulmonary passage and expressed as 1) substrate metabolism (M), 2) Amax/Km (Amax being equal to the product of enzyme mass and the constant of product formation), and 3) (Amax/Km)/100 ml blood flow. When respiratory acidosis/alkalosis was produced by altering respiratory rate at constant airway pressure, substrate (BPAP) utilization varied proportionally to arterial pH and inversely proportionally to arterial PCO2 (PaCO2) (P less than 0.05). Percent BPAP metabolism (%M) ranged from 92 +/- 3 (respiratory alkalosis) to 85 +/- 3 (normal), 82 +/- 3 (respiratory acidosis), and 78 +/- 2% (severe respiratory acidosis). Amax/Km similarly decreased from 899 +/- 129 to 825 +/- 143, 601 +/- 74, and 450 +/- 34 ml/min, respectively, and (Amax/Km)/100 ml blood flow was reduced from 176 +/- 26 to 131 +/- 22, 111 +/- 12, and 97 +/- 5, respectively. However, when respiratory acidosis/alkalosis was produced by altering both respiratory rate and airway pressure, no changes were observed in either %M, Amax/Km or (Amax/Km)/100 ml blood flow. Similarly metabolic alkalosis or acidosis did not alter M, Amax/Km or (Amax/Km)/100 ml blood flow. These results indicate that pulmonary endothelial ACE function can be affected by acid-base disturbances, probably indirectly through changes in perfused microvascular surface area.

Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment.

The parameter Amax/Km (product of reactant enzyme mass in perfused microvessels and the constant kcat/Km), calculated from in vivo assays of pulmonary endothelial ectoenzymes (e.g., angiotensin-converting enzyme, ACE), can provide estimates of the perfused pulmonary microvascular surface area (PMSA) in the absence of enzyme dysfunction. We examined the relationship between PMSA and pulmonary blood flow (Qb) in anesthetized rabbits placed on total heart bypass, using [3H]benzoyl-Phe-Ala-Pro (BPAP) as the ACE substrate. When Qb was increased from 250 to 1,100 ml/min, at zone 3 conditions, pulmonary arterial pressure increased, pulmonary vascular resistance (PVR) decreased, and Amax/Km increased linearly, reflecting increasing PMSA. When only the left lung was perfused, increasing Qb from 250 to 636 +/- 17 ml/min (the last value representing fully recruited and/or distended vascular bed), PVR decreased, while Amax/Km increased. When Qb was further increased to 791 +/- 44 ml/min, both PVR and Amax/Km remained unchanged, confirming the lack of additional changes in PMSA. We conclude that Amax/Km provides a sensitive indication of PMSA, because it 1) increases with increasing Qb and decreasing PVR, 2) reaches a maximum at Qb values that correspond to the minimal values in PVR, and 3) like PVR, did not change with further increases in Qb. Compared with predicted changes in PMSA produced by either microvascular recruitment alone or distension alone, our data indicate that recruitment is a larger contributor to the observed increase in PMSA.

Effects of alveolar pressure on lung angiotensin-converting enzyme function in vivo.

Angiotensin-converting enzyme lines the luminal surface of pulmonary capillary endothelial cells. The metabolism of its synthetic substrate, 3H-benzoyl-L-phenylalanyl-L-alanyl-L-proline ([3H]BPAP) has been used as an indicator of pulmonary microvascular function. Because the flow-volume status of the pulmonary capillaries is dependent on intra-alveolar pressure, we have studied the effects of airway pressure on endothelial plasmalemmal angiotensin-converting enzyme function in rabbit lungs in vivo. Static inflation of the lungs to a pressure of 0 or 5 Torr did not change percent transpulmonary metabolism and Amax/Km ratio (defined as E X Kcat/Km and thus, under normal conditions, an indirect measure of perfused endothelial luminal surface area) compared with control measurements during conventional mechanical ventilation. When the inflation pressure was increased to 10 Torr, percent metabolism of [3H]BPAP remained unaltered but Amax/Km decreased to 60% of the control value. This decrease was in close relation to the decrease in pulmonary blood flow. Addition of 5 cmH2O positive end-expiratory pressure (PEEP) to the mechanical ventilation also decreased Amax/Km values and pulmonary blood flow but did not influence percent metabolism of [3H]BPAP. These results suggest that the detected alterations in apparent enzyme kinetics were more likely due to hemodynamic changes than to alterations in angiotensin-converting enzyme function. Thus high static alveolar pressures as well as PEEP probably reduced the fraction of perfused microvessels as reflected in changes in Amax/Km ratios. This information should prove useful in interpreting the response of pulmonary endothelial enzymes to injury.

Inhaled NO and prostacyclin during porcine single lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI2) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft. METHODS: Eighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI2 (25 microg/mL/30 minutes, 50 microg/mL/30 minutes), or no drugs (control). RESULTS: In the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI2 groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI2. Neither drug improved oxygenation in the graft. CONCLUSIONS: Nitric oxide and PGI2 decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.

Prostaglandin E1 or prostacyclin in Euro-Collins solution fails to improve lung preservation.

BACKGROUND: In search of the ideal composition of the flush solution for pulmonary preservation, we studied the effects of prostaglandin E1 (PGE1) and prostacyclin as an additive to Euro-Collins solution (ECS) on pulmonary hemodynamics and gas exchange in a porcine single lung transplantation model using extracorporeal circulation and right heart bypass. METHODS: Twenty-two pigs served as donors. The animals were randomized to receive either modified ECS alone (control group, n = 8), ECS with 100 micrograms/L of PGE1 (PGE1 group, n = 6), or ECS with 200 micrograms/L of prostacyclin (prostacyclin group, n = 8). Left lung transplantation was performed in 22 recipients after approximately 4 hours of cold ischemia. RESULTS: Carbon dioxide elimination was significantly depressed in the two prostaglandin groups, and the use of PGE1 was associated with a significant decrease in arterial oxygen tension compared with the control group. Both drugs were inefficient in alleviating the increase in pulmonary vascular resistance after transplantation. CONCLUSION: The use of prostaglandins as constituents of the flush solution was not followed by any improvement of early graft function after cold ischemia.

Successful treatment of mediastinal gas gangrene due to esophageal perforation.

Esophageal perforation and mediastinal gas gangrene developed in a 55-year-old male after the endoscopic ethanol injection of a Mallory-Weiss ulcer. Initially, extensive gangrene of the esophagus and the mediastinum was treated by esophagectomy; however, an abundance of Clostridium perfringens in the Gram stain verified the presence of gas gangrene. Subsequently, the patient was transferred to a hyperbaric oxygen center, wherein a total of seven hyperbaric treatments were administered. The patient survived, and 4 months later, after having undergone several reoperations because of pleural empyema, mediastinal abscess, splenic rupture, and acalculous cholecystitis, was discharged and is still surviving.

Cigarette smoke affects lipolytic activity in isolated rat lungs.

Isolated perfused rat lungs liberated fatty acids at a rate of 15 mumol/hr during perfusion of triglyceride-rich medium through the pulmonary vascular bed. About 80% of this activity seemed to result from lipoprotein lipase and 20% to hormone-sensitive lipase. Ventilation of the lungs with cigarette smoke instead of air during the perfusion reduced fatty acid liberation by 23%. Pre-exposure of rats to cigarette smoke for either 1 or 10 days did not cause significant changes in lung lipolytic activity compared to sham-exposed controls.

Skin dose calculations for uranium fuel particles below 500 microns in diameter.

Two different methods for skin dose calculations, VARSKIN Mod 2 and PSS are compared for a spherical uranium fuel particle (diameter 1-500 microns) deposited on the skin. Nuclide-specific beta dose rate at different skin depths for a particle of unit activity is determined as a function of particle size. Both methods show that the effects of self-shielding must be included in the dose calculations for low and medium energy beta emitters. Skin dose rate is drastically overestimated when point source approximation is used. For high energy beta emitters (e.g., 90Y, 106Rh, and 144Pr) the volume source can be approximated as a point source. The difference in doses is then below 20% for particles up to 100 microns in diameter. The models give equal results deep in the skin (in terms of range of the beta particles). The reason is that the correction due to the diminished backscattering in air-tissue interface is insignificant at large distances. For three-dimensional sources the backscattering correction should be introduced in the VARSKIN Mod 2.