Small Lungs Research Articles

DYSANAPSIS

Dear Editor-in-Chief: We read with interest the article by Dominelli et al. (1). They present data on dysanapsis and its potential contribution to obtaining expiratory flow limitation during exercise. We agree that dysanapsis may be an important concept regarding the presence of expiratory flow limitation and suggest that it integrates many of the basic principles related to the determination of maximal expiratory flow. These are well stated by Mead (4): “Persons with large lungs do not necessarily have larger airways than do persons with small lungs” and “…maximal expiratory flow is sensitive to lung recoil as well as airway size…” and “For example, a person with a high lung recoil at 50% of forced vital capacity would have a higher flow than would someone with airways of the same size but a lower lung recoil at 50% forced vital capacity (FVC).” Thus, a calculation of dysanapsis (FEF50/[FVC × Pst(l)50]) takes into account the basic interrelationships of flow, volume, and lung recoil pressure, which are so important in the determination of maximal expiratory flow and expiratory flow limitation (2–5). We are concerned that the calculation of dysanapsis using predicted lung recoil will not accurately reflect true dysanapsis in all individuals. As seen in Figure 1 in the original article by Mead (4), plotting flow at 50% of vital capacity against vital capacity has a wide scatter. It is only when the relationship of flow and lung volume is adjusted by individual measurements of lung recoil that the scatter is removed (Fig. 2C in Mead [4]). Likewise, we believe that Figure 4 presented by Dominelli et al. (1) could be quite different if individual measurements of lung recoil were used in the calculation of dysanapsis. The decisive question is whether the reduced flow in the one group of women is accompanied by a decrease in lung recoil pressure or by a normal pressure. In the article, each subject is assumed to have a predicted normal pressure. Adjusting the individual predicted pressures by just the SE of the measure (±1.39 cm H2O) could have a large effect on the individual estimate of dysanapsis. Thus, we believe the dysanapsis values presented by the authors could be grossly misleading. Applying a truly random error to all subjects (means equal zero), as the authors suggested, will not reduce the difference between the two groups. A simpler explanation for their findings is that the expiratory flow limitation (EFL) group had a higher degree of “scooping” on their expiratory flow–volume curves compared with the nonexpiratory flow limitation (NEFL) group (Table 1, where expiratory flows are lower in the EFL group). It would be worthwhile to probe further into the early history of either lung infections or childhood asthma in these groups. Plus, it would have been informative to know if total lung capacity was also reduced in the EFL group, which might help explain why the authors found the subjects with expiratory flow limitation to breathe at a lower end-expiratory lung volume contrary to findings in normal and patient populations studied. Tony G. Babb, PhD Presbyterian Hospital of Dallas Dallas, TX Kenneth C. Beck, PhD KCBeck Physiological Consulting, LLC Liberty, UT Bruce D. Johnson, PhD Mayo Clinic Rochester, MN The authors declare no conflicts of interest.

SU-E-T-564: Radiation Therapy for Lung Cancer: A Treatment Planning Comparison among Fixed Field IMRT, Coplanar and Noncoplanar Arcs Volumetric Modulated Arc Therapy.

A treatment planning study was performed to compare fixed field IMRT, coplanar and noncoplanar VMAT. Treatment planning CT scans of three lung cancer patients with small (2244cc), medium (2845cc) and large (3531cc) lungs were used to create simulated patient cases. For each simulated patient, three spherical tumors (GTV) of varying diameters: 1, 3, 5 cm were contoured onto lung CT scans. The ITV was set as GTV+2 cm and the PTV was set as ITV+1 cm. The location of the tumor was set in the right middle lobe of lung. For each patient scenario, the IMRT (nine static fields), single coplanar arc VMAT and 5 noncoplanar arcs VMAT treatment plans were generated using Pinnacle treatment planning system. The arcs of noncoplanar VMAT were set at -30° (clockwise and counterclockwise), 0° and 30° (clockwise and counterclockwise). Thetreatment plans were evaluated by calculation of V100%, V80%, V50% and V20%, DVH of dose constrain rings (DCR) at PTV+1cm, +2cm, +3cm, +4cm and Paddick Conformity Index (CI: 0-1 best) and Gradient Index (GI:the smaller the better). The V100% and V80% were similar for all the plans but the V50% and V20% were the largest for IMRT, and the smallest for noncoplanar VMAT. The noncoplanar VMAT had larger V<20but smaller V>20 for all the DCRs comparing to the other two plans. The CI of noncoplanar VMAT was slightly larger than the other two plans. The GI was the smallest for noncoplanar VMAT and the largest for IMRT for all the simulation scenarios. The noncoplanar VMAT consistently provides high dose conformity to the target and low dose to healthy tissue. The noncoplanar VMAT has larger low dose volume while smaller high dose volume comparing to IMRT and coplanar VMAT.

Successful treatment of patients with paraquat intoxication: three case reports and review of the literature

To report on three patients with paraquat (PQ) intoxication surviving after combined therapy with hemoperfusion (HP), cyclophosphamide (CTX), and glucocorticoid. Three patients suffered acute renal failure in a few days after ingesting a lethal amount of PQ. Chest computed tomography (CT) scans revealed obvious pulmonary inflammation, pleural effusion, and fibrous lesions several days after ingestion. HP was performed immediately, followed by large doses of glucocorticoid (methylprednisolone, 500 g/d) and CTX (approximately 4 g). After 50 d of treatments, all three patients were discharged in healthy condition, with chest CT showing small fibrous lesions, exudation, and both lungs clear of auscultation. The protective effect of the lungs may have been due to timely treatment at adequate doses.

Comparison of internal dosimetry factors for three classes of adult computational phantoms with emphasis on I-131 in the thyroid

The S values for 11 major target organs for I-131 in the thyroid were compared for three classes of adult computational human phantoms: stylized, voxel and hybrid phantoms. In addition, we compared specific absorbed fractions (SAFs) with the thyroid as a source region over a broader photon energy range than the x- and gamma-rays of I-131. The S and SAF values were calculated for the International Commission on Radiological Protection (ICRP) reference voxel phantoms and the University of Florida (UF) hybrid phantoms by using the Monte Carlo transport method, while the S and SAF values for the Oak Ridge National Laboratory (ORNL) stylized phantoms were obtained from earlier publications. Phantoms in our calculations were for adults of both genders. The 11 target organs and tissues that were selected for the comparison of S values are brain, breast, stomach wall, small intestine wall, colon wall, heart wall, pancreas, salivary glands, thyroid, lungs and active marrow for I-131 and thyroid as a source region. The comparisons showed, in general, an underestimation of S values reported for the stylized phantoms compared to the values based on the ICRP voxel and UF hybrid phantoms and relatively good agreement between the S values obtained for the ICRP and UF phantoms. Substantial differences were observed for some organs between the three types of phantoms. For example, the small intestine wall of ICRP male phantom and heart wall of ICRP female phantom showed up to eightfold and fourfold greater S values, respectively, compared to the reported values for the ORNL phantoms. UF male and female phantoms also showed significant differences compared to the ORNL phantom, 4.0-fold greater for the small intestine wall and 3.3-fold greater for the heart wall. In our method, we directly calculated the S values without using the SAFs as commonly done. Hence, we sought to confirm the differences observed in our S values by comparing the SAFs among the phantoms with the thyroid as a source region for selected target organs—small intestine wall, lungs, pancreas and breast—as well as illustrate differences in energy deposition across the energy range (12 photon energies from 0.01 to 4 MeV). Differences were found in the SAFs between phantoms in a similar manner as the differences observed in S values but with larger differences at lower photon energies. To investigate the differences observed in the S and SAF values, the chord length distributions (CLDs) were computed for the selected source–target pairs and compared across the phantoms. As demonstrated by the CLDs, we found that the differences between phantoms in those factors used in internal dosimetry were governed to a significant degree by inter-organ distances which are a function of organ shape as well as organ location.

Multiple organ inflammatory response to portosystemic shunt in the rat

Portosystemic shunt surgery is the best procedure to prevent recurrent bleeding of esophageal varices, but carries a high risk of postoperative inflammatory complications, including hepatic encephalopathy. Thus, portosystemic shunting procedures could induce a systemic inflammatory response with multiple organ dysfunction syndrome, including hepatic encephalopathy. To verify this hypothesis we used male Wistar rats at 6weeks of postoperative evolution: Control (CR; n=14), Sham-operated (SO; n=8) and rats with end-to-side portacaval shunt (PCS; n=15). TNF-α, IL-1β and IL-10 were assayed by ELISA techniques, the expression of the endothelial constitutive nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), constitutive and inducible heme-oxygenase (HO-1 and HO-2) were assayed by Western-blot. mRNA levels of HO-1, HO-2, TNF-α, IL-1β and IL-10 were quantified by reverse transcriptase polymerase chain reaction amplification (RT-PCR) in the small bowel, liver, spleen and lungs. Portacaval shunting in the rat produces an interorgan imbalance of pro- and anti-inflammatory mediators. TNF-α mRNA expression is decreased in the liver (0.69±0.28, p<0.05). The hepatic production of IL-Iβ (204.13±71.90pg/100g; p<0.001) and IL-10 (4505.47±337.97pg/100g; p<0.001) is also decreased. However, the intestinal pro-inflammatory (TNF-α: 1471.86±153.62pg/100g, p<0.001; IL-1β: 48.35±9.84pg/100g, p<0.001 and iNOS: 0.59±0.01, p<0.01) and anti-inflammatory (IL-10: 1503.39±53.5pg/100g, p<0.001 and HO-1: 2.23±0.16, p<0.001) mediators are increased. Total portacaval shunting in the rat induces impairments of pro- and anti-inflammatory mediators in the splanchnic–lung axis that could be associated with a multiple organ dysfunction syndrome. Therefore, the complications after portosystemic shunts could be integrated into a systemic inflammatory response of possible intestinal origin.

Comparative Efficacy of Trichlorphon and Trichlorphon/Ivermectin Combination Treatment against Anthelmintic-Resistant Cattle Nematodes in Argentina

Twenty-four Holando Argentino male calves were treated orally with 50 mg/kg body weight trichlorphon (TCF); 0.2 mg/kg body weight subcutaneous ivermectin (IVM); a combination of TCF+IVM at the same doses and administration routes; or remained untreated (control group). All calves were necropsied at day 14 post treatment for counting and identification of worms from abomasum, small and large intestines and lungs to determine the absolute efficacy (controlled efficacy test) for each treatment. Using the faecal egg count reduction test, the efficacy was 63.7 % for TCF, 72.3 % for IVM and 99.2 % for TCF+IVM. The absolute efficacy of IVM and IVM+TCF was 100 % against Haemonchus placei, Trichostrongylus axei and Ostertagia ostertagi (p < 0.05). TCF showed a similar level of efficacy except against O. ostertagi (84.7 %). Efficacy of the treatments against Cooperia oncophora/pectinata/mcmasteri was 80.4 % for IVM, 95.7 % for TCF and 99.6 % for TCF+IVM; against Trichostrongylus colubriformis was 79 % for IVM, 86.2 % for TCF and 94.1 % for TCF+IVM; against Nematodirus helvetianus was 0 % for IVM, 100 % for TCF and 93.8 % for TCF+IVM. The efficacies of TCF, IVM and TCF+IVM were 100 % against Oesophagostomum radiatum and Trichuris spp. The efficacy of TCF against Dictyocaulus viviparus was 52 % and 100 % for IVM and IVM+TCF, respectively. This is the first report of Trichostrongylus colubriformis and Nematodirus helvetianus resistant to ivermectin treatment in cattle of Argentina. The TCF+IVM combination could be an alternative for the control and treatment of nematode infections including IVM-resistant strains.

Lung morphometry with hyperpolarized 129Xe: Theoretical background

The (3) He lung morphometry technique, based on MRI measurements of hyperpolarized (3) He gas diffusion in lung airspaces, provides unique information on the lung microstructure at the alveolar level. In vivo 3D tomographic images of standard morphological parameters (airspace chord length, lung parenchyma surface-to-volume ratio, and number of alveoli per unit volume) can be generated from a rather short (several seconds) MRI scan. The technique is based on a theory of gas diffusion in lung acinar airways and experimental measurements of diffusion-attenuated MRI signal. The present work aims at developing the theoretical background of a similar technique based on hyperpolarized (129) Xe gas. As the diffusion coefficient and gyromagnetic ratio of (129) Xe gas are substantially different from those of (3) He gas, the specific details of the theory and experimental measurements with (129) Xe should be amended. We establish phenomenological relationships between acinar airway geometrical parameters and the diffusion-attenuated MR signal for human and small animal lungs, both normal lungs and lungs with mild emphysema. Optimal diffusion times are shown to be about 5 ms for human and 1.3 ms for small animals. The expected uncertainties in measuring main morphometrical parameters of the lungs are estimated in the framework of Bayesian probability theory.

MO-F-110-07: Comparison of S Values for Three Classes of Adult Computational Phantoms for I-131 in the Thyroid

Purpose: To compare S values for three classes of adult computational phantoms for Iodine-131 in the thyroid. Methods: S values between the thyroid (source organ) containing I-131 and important target organs were compared for three classes of computational human phantoms: stylized (mathematical), voxel and hybrid. S values were calculated for International Commission on Radiological Protection (ICRP) reference adult voxel phantoms and the University of Florida (UF) adult hybrid phantoms by using the Monte Carlo transport code MCNPX2.5, and compared with S values derived 30 years ago at the Oak Ridge National Laboratory (ORNL) for their stylized phantom but using a different transport code. Eleven target organs were selected for comparison: brain, breast, stomach wall, small intestine wall, colon wall, heart wall, pancreas, salivary glands, thyroid, lungs, and active marrow. We also computed and compared specific absorbed fractions (SAF) and chord length distributions (CLD) among the phantoms for source and target organ-pairs. Results: Our analysis showed on average, an underestimation of S values and, consequently, of organ doses for the ORNL stylized phantoms compared to the ICRP and UF phantoms. Inter-organ distance and organ shape differences were identified as the main cause of the differences. Conclusions: The ICRP and UF phantoms are considered to more realistically model the human anatomy than the ORNL stylized phantoms. Therefore, the S value differences likely arise from unrealistic locations and shapes of the thyroid and target organs in the stylized phantoms. In addition, the S value differences between ICRP and UF phantoms illustrate there can be differences among phantoms designed to match the ICRP reference anatomy data, which suggests that human variability has not yet been fully described. This comparison indicates the value of the newer generation phantoms for conducting more reliable internal dosimetry.

Microsporidia in exotic birds: Intermittent spore excretion of Encephalitozoon spp . in naturally infected budgerigars ( Melopsittacus undulatus)

Nine naturally infected asymptomatic budgerigars ( Melopsittacus undulatus) were screened daily for microsporidia spore excretion during a 30-day period and the localization of infection was evaluated using microscopy and molecular methods. While the microscopic examination revealed 2.4% positivity out of all fecal samples, using PCR the positivity was 10× higher (24.6%). All nine budgerigars excreted microsporidial spores intermittently in irregular intervals with 1–11-day long interruptions. Most of the birds were infected simultaneously with Encephalitozoon cuniculi and Encephalitozoon hellem. While histological and TEM examination failed to confirm the presence of microsporidial spores in tissues, the PCR detected microsporidial DNA mostly in the small intestine, liver and lungs of four selected budgerigars dissected. Despite the chronic infection proved using molecular methods, no clinical signs of disease were observed during monitoring and no pathological findings were found during dissection.

Characterization of postnatal expression of rat MFG‐E8 gene in intestines, liver and lungs

MFG‐E8 (milk fat globule‐EGF factor 8) plays an important role in tissue remodeling, clearance of apoptotic cells, and intestinal epithelial wound healing. Here, we examined the expression of MFG‐E8 mRNA in the small intestine, liver and lungs during postnatal development. Briefly, Sprague‐Dawley rats were sacrificed at different ages (E20, P0, P5, P10 and P21). Total RNA was extracted from various tissues including the small intestine, liver and lungs. The MFG‐E8 gene expression was quantified by real‐time PCR. We found that the MFG‐E8 gene was expressed at a low level on E20 in the liver. Within 24 h after birth, its expression was increased 2.57 fold (P&lt;0.01). It was then stably expressed at high level during the postnatal period. In contrast, in the small intestine, MFG‐E8 gene significantly decreased 2.88 fold (P&lt;0.01) within 24 h after birth compared to E20, then it gradually regained E20 values on P10. The gene was persistently expressed until P21. In the lungs, MFG‐E8 is constitutively expressed prenatally at E20. Its expression did not change during the postnatal period. In conclusions, our study indicated that MFG‐E8 is extensively expressed in the small intestine, liver, and lungs. As opposed to other organs, the expression of intestinal MFG‐E8 is decreased during the first week of life. However, the physiological meaning of MFG‐E8 gene expression pattern in postnatal stage remains to be determined.

Gefitinib Increases Serum Concentrations of Oral Irinotecan and SN-38 without Increasing the Biliary Concentration of SN-38 in Rats

Background: Gefitinib competes with topoisomerase I inhibitors at drug efflux pumps in vitro. We evaluated the effects of oral gefitinib on pharmacokinetic parameters of orally coadministered irinotecan. Methods: We measured the serum pharmacokinetic parameters and biliary excretion of irinotecan, SN-38 and its glucuronide after irinotecan (50 or 100 mg/kg) was orally administered with or without gefitinib 100 mg/kg to rats. We measured the concentrations of irinotecan and SN-38 in the small intestine, liver, lungs and kidneys in each rat. Results: The plasma area under the curve (0–24 h) of irinotecan and SN-38 was increased significantly, while the apparent elimination constant of irinotecan was decreased significantly. Gefitinib significantly increased the biliary cumulative amounts of irinotecan, but not of SN-38, and also influenced the enterohepatic circulation of irinotecan, but not of SN-38. Conclusions: Gefitinib increased the serum concentrations of irinotecan and SN-38 following oral administration of irinotecan without increasing the biliary excretion of SN-38 in vivo.

CCR2 Receptor Is Essential to Activate Microbicidal Mechanisms to Control Toxoplasma gondii Infection in the Central Nervous System

Chemokines comprise a structurally related family of cytokines that regulate leukocyte trafficking. Because infection with Toxoplasma gondii can induce an important inflammatory reaction that, if left uncontrolled, can lead to death, we investigated the role of the chemokine receptor CCR2 in T. gondii infection. We orally infected CCR2(-/-) mice with five ME-49 T. gondii cysts and monitored morbidity, survival, and immune response thereafter. The CCR2(-/-) mice displayed higher susceptibility to infection as all mice died on day 28 after infection. Despite similar Th1 responses, a more evident anti-inflammatory response was induced in the peripheral organs of CCR2(-/-) mice compared with wild-type C57BL/6 mice. Additionally, CCR2(-/-) mice presented greater parasitism and a milder inflammatory reaction in their peripheral organs with lesser CD4(+) and MAC-1(+) and greater CD8(+) cell migration. The parasite load decreased in these organs in CCR2(-/-) mice but remained uncontrolled in the central nervous system. Additionally, we observed down-regulated inducible nitric oxide synthase expression in peripheral organs from CCR2(-/-) mice that was associated with a small nitric oxide production by spleen macrophages. In conclusion, in the absence of CCR2, another mechanism is activated to control tissue parasitism in peripheral organs. Nevertheless, CCR2 is essential for the activation of microbicidal mediators that control T. gondii replication in the central nervous system.

Cleft Palate in a Male Water Buffalo Calf

Congenital palatal defects are common in animals but there is only one report of water buffalo has been recorded in Iran. One died male water buffalo calf was examined after hysterotomy operation. At necropsy findings, brachygnathia, palate cleft and small lungs were diagnosed. It is the second report of water buffalo cleft palate in Iran.

Endotoxin exposure, wheezing, and rash in infancy in a New Zealand birth cohort

Wheezing in infancy is common and is associated with small lungs, viral respiratory tract infection, and environmental tobacco smoke exposure. Recently, increased levels of endotoxin in the domestic environment have also been associated with infant wheezing, particularly among infants with a family history of atopic disease. To explore associations between exposure to endotoxin at 3 months of age and reported symptoms of wheezing, rhinitis, itchy scaly rash, and atopy at 15 months in a birth cohort of 881 New Zealand children. Using standardized methods, a 1-m(2) site from the bedroom floors of the 3-month-old infants was sampled and analyzed for endotoxin. Wheezing was significantly associated with higher endotoxin levels (odds ratio [OR], 1.54; 95% CI, 1.03-2.30), particularly among infants with a parental history of allergic disease (OR, 1.67; 95% CI, 1.07-2.60). Higher endotoxin concentrations were also strongly associated with recurrent itchy rashes (OR, 1.87; 95% CI, 1.14-3.05), particularly among infants who were atopic (OR, 4.64; 95% CI, 1.56-13.77) or had a parental history of allergic disease (OR, 2.10; 95% CI, 1.22-3.61). Domestic endotoxin was associated with reported airway and skin symptoms in this large group of New Zealand infants. The role of endotoxin in the development of respiratory and skin disease in infancy deserves further study. Reducing domestic endotoxin exposure might reduce infant wheezing and atopic dermatitis, but the long-term benefits of this remain unclear.

The effect of changing ventilator settings on indices of ventilation inhomogeneity in small ventilated lungs

BackgroundIn ventilated newborns the use of multiple breath washout (MBW) techniques for measuring both lung volume and ventilation inhomogeneity (VI) is hampered by the comparatively high dead space fraction. We studied how changes in ventilator settings affected VI indices in this particular population.MethodsUsing a computer simulation of a uniformly ventilated volume the interaction between VI indices (lung clearance index (LCI), moment ratios (M1/M0, M2/M0, AMDN1, AMDN2) of the washout curve) and tidal volume (VT), dead space (VD) and functional residual capacity (FRC) were calculated. The theoretical results were compared with measurements in 15 ventilated piglets (age <12 h, median weight 1135 g) by increasing the peak inspiratory pressure (PIP). FRC and VI indices were measured by MBW using 0.8% heptafluoropropane as tracer gas.ResultsThe computer simulation showed that the sensitivity of most VI indices to changes in VD/VT and VT/FRC increase, in particular for VD/VT > 0.5. In piglets, the raised PIP caused a significant increase of VT from 15.4 ± 9.5 to 21.9 ± 14.7 (p = 0.003) and of the FRC from 31.6 ± 14.7 mL to 35.0 ± 15.9 mL (p = 0.006), whereas LCI (9.15 ± 0.75 to 8.55 ± 0.74, p = 0.019) and the moment ratios M1/M0, M2/M0 (p < 0.02) decreased significantly. No significant changes were seen in AMDN1 and AMDN2. The within-subject variability of the VI indices (coefficient of variation in brackets) was distinctly higher (LCI (9.8%), M1/M0 (6.6%), M2/M0 (14.6%), AMDN1 (9.1%), AMDN2 (16.3%)) compared to FRC measurements (5.6%). Computer simulations showed that significant changes in VI indices were exclusively caused by changes in VT and FRC and not by an improvement of the homogeneity of alveolar ventilation.ConclusionIn small ventilated lungs with a high dead space fraction, indices of VI may be misinterpreted if the changes in ventilator settings are not considered. Computer simulations can help to prevent this misinterpretation.

Functional residual capacity measurement by heptafluoropropane in ventilated newborn lungs: In vitro and in vivo validation

Heptafluoropropane is an inert gas commercially used as propellant for inhalers. Since heptafluoropropane can be detected in low concentrations, it could also be used as a tracer gas to measure functional residual capacity and ventilation homogeneity. The aim of the present study was to validate functional residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%) during mechanical ventilation in small, surfactant-depleted lungs using a newborn piglet model. Prospective laboratory and animal trial. Animal laboratory in a university setting. Sixteen newborn piglets (age<12 hrs, median weight 1390 g [705-4200 g]) before and after surfactant depletion (Pao2<100 torr in Fio2=1.0) by lung lavage. Heptafluoropropane was measured with a new infrared mainstream sensor connected with the flow sensor of the Dräger Babylog 8000. Accuracy and precision of the measurement technique were tested in a mechanical lung model with a volume range from 11 to 35 mL. Reproducibility of the method and its sensitivity to detect changes of functional residual capacity were assessed in vivo by variation of ventilatory variables. In vitro the absolute error of functional residual capacity was <1 mL (relative errors<3%) with a coefficient of variation<4%. The coefficient of variation of consecutive in vivo measurements was only slightly higher (<5.1%). Measurement of heptafluoropropane concentrations in blood showed no significant accumulation for repeated functional residual capacity measurements within short time periods. After lung lavage, the functional residual capacity decreased from 20.9 mL/kg to 14.5 mL/kg (p<.05) despite increased ventilatory pressures, and lung clearance index (p<.001) and moment ratios (p<.01) increased significantly due to uneven alveolar ventilation. In healthy lungs, the increase in peak inflation pressure and positive end-expiratory pressure by 3-4 cm H2O had only a moderate effect on functional residual capacity (20.9+/-8.6 vs. 26.0+/-11.9 mL/kg, p=.17) and no effect on ventilatory homogeneity, whereas in surfactant-depleted lungs the functional residual capacity increased from 14.5+/-6.7 mL/kg to 29.9+/-12.6 mL/kg (p<.001) and lung clearance index and moment ratios decreased significantly (p < .01). Heptafluoropropane is a suitable tracer gas for precise functional residual capacity measurements tested in vitro and allows for reproducible measurements in ventilated small lungs without any adverse effects on mechanical ventilation. The sensitivity of the method is sufficiently high to demonstrate the effect of changes in ventilatory settings on the functional residual capacity and ventilation homogeneity.

Small lungs and suspect smooth muscle: congenital diaphragmatic hernia and the smooth muscle hypothesis

Lung hypoplasia and congenital diaphragmatic hernia (CDH) represent an unsolved clinical and scientific problem. Early lung morphogenesis is coupled to development and function of pulmonary smooth muscle. Activity of the latter is abnormal from the earliest stages of hypoplastic lung development and before supervening CDH. A “smooth muscle hypothesis” is advanced to help explain embryonic lung malformations, fetal failure of lung growth, and postnatal susceptibility to barotrauma, airway hyperreactivity, and pulmonary hypertension in CDH. Exploring the interaction of smooth muscle function and airway pressures may help optimise tracheal occlusion and provide support for both an adequately powered trial of glucocorticoids and also for experimental “preventilation” strategies in fetal CDH.

Immunomodulatory and Anti-Inflammatory Activity Induced by Oral Administration of a Probiotic Strain of Lactobacillus Casei

The aim of this work was to study the effect of the long-term cyclic administration of the probiotic strain of Lactobacillus ( L.) casei CRL 431 as a mucosal immunomodulator of the immune cells associated with the lamina propria of the small intestine, bronchus and other immune cells not associated with mucosal tissues, such as peritoneal macrophages. BALB/c mice were orally administered with a suspension of Lc 109 cfu/day/animal in non-fat milk (NFM) 10% for two consecutive days, the optimal dose selected in previous studies to reach protective immunity. This administration was repeated cyclically every 5 days for 98 days. Mice in the control group received only NFM 10%. Samples were taken after two days of L. casei administration and every 14 days until day 98. The small intestine and lungs were removed for histological slices preparation. Haematoxilin-eosin stains were made for histological studies of the small intestine. The number of IgA producing cells in the lamina propria of the small intestine and in bronchus was determined by immunofluorescence assays. Regulatory (IL-4, IL-10) and proinflammatory (TNF-α, INF-γ) cytokines were measured in the gut. Peritoneal macrophages were collected during the same periods for phagocytosis assays. We determined an increase in the number of IgA+ cells in the lamina propria of the small intestine in all the periods assayed and in BALT only until day 28. The cytokines studied (IL-10, IL-4, TNF-α and INF-γ) increased in most of the periods assayed, the effect being more remarkable for the anti-inflammatory cytokines such as IL-4 and IL-10. INF-γ was also increased but no modifications in the histological studies of the small intestine were observed, suggesting other roles for this cytokine The phagocytic activity of PM increased for most of the periods assayed. We demonstrated that long-term cyclic oral L. casei administration favors mucosal immunity and modulates the immune response to maintain the homeostasis at the mucosal level.

Parasites of two lizard species, Anolis punctatus and Anolis transversalis (Squamata: Polychrotidae) from Brazil and Ecuador

Parasites of two lizard species, Anolis punctatus and Anolis transversalis (Squamata: Polychrotidae) from Brazil and Ecuador Stephen R. Goldberg 1 , Charles R. Bursey 2 , Laurie J. Vitt 3 Anolis punctatus and Anolis transversalis , ar- boreal anoles, are considered to be the “crown giants” among Amazonian anoles (Vitt et al., 2003a). Crown giants are anoles with body sizes substantially larger than those of congeners occurring on tree trunks and on the ground (Williams, 1972). Although both species appear to forage in the crown, A. punctatus is most eas- ily observed at the crown-trunk interface. Morphologically, A. punctatus fits the bau- plan of typical crown giant anoles (Irschick et al., 1997); A. transversalis is similar, but not used in the analysis. Individuals of these two species are about the same size, A. transver- salis slightly smaller and restricted to undis- turbed primary forest more so than A. puncta- tus , but both use similar microhabitats and have similar diets, volumetrically, A. punctatus ate mostly ants and orthopterans, A. transversalis ate mostly roaches, beetles, and ants (Vitt et al., 2003a). Both species occur in the Amazonian regions of Brazil, Colombia, Ecuador, and Peru (Avila-Pires, 1995). Helminths of A. punctatus from Peru have been reported (Bursey et al., 2005), but to our knowledge, helminth parasites of A. transversalis are unknown. The purpose of this paper is to report helminths of A. punctatus 1 - Whittier College, Department of Biology, Whittier, California 90608, USA e-mail: sgoldberg@whittier.edu 2 - Pennsylvania State University, Shenango Campus, De- partment of Biology, Sharon, Pennsylvania 16146, USA 3 - Sam Noble Oklahoma Museum of Natural History and Zoology Department, University of Oklahoma, Norman, Oklahoma 73072, USA and A. transversalis and examine these data in relation to the ecology of the lizard species. Twenty-one Anolis punctatus (mean snout-vent length [ SVL ] = 70 . 4 ± 6 . 6 mm, range: 57-83 mm) and 17 Anolis transversalis (SVL = 69 . 0 ± 11 . 6 mm, range: 48-83 mm) were borrowed from the herpetology collection of the Sam Noble Oklahoma Museum of Natural History (OMNH) and examined for helminths. These anoles had previously been utilized in an ecological study during which stomachs were removed to determine diet (Vitt et al., 2003a). Thus stom- achs were not available for this study. Collection locali- ties are as follows: A. punctatus , 11 (OMNH 37392-37402), Rondonia State, Brazil, 1998; eight (OMNH 37167-37173, 37676), Amazonas State, Brazil, 1997 (n = 7) and 1999 (n = 1); two (OMNH 40412-40413), Sucumbios Province, Ecuador, 1993, 1994; A. transversalis , five (OMNH 37029- 37033), Acre State, Brazil, 1996; eight (OMNH 37045, 37403-37410), Rondonia State, Brazil, 1998; four (OMNH 37677-37680), Amazonas State, Brazil, 1998. These anoles had originally been fixed in 10% formalin and stored in 70% ethanol. The small intestine, large intestine and lungs were removed and searched for helminths using a dissecting mi- croscope. The coelom was also searched. Each nematode was cleared in glycerol on a glass slide and identified with a light microscope. Cestodes were stained with hematoxylin, mounted in Canada balsam and examined as a whole mount. Helminth species, number of helminths, prevalence (in- fected lizards/total lizards examined × 100), mean intensity (mean number helminths per infected lizard) and range are found in table 1. In the text the means are followed by ± one SD. Helminths were deposited in the United States Na- tional Parasite Collection (USNPC), Beltsville, Maryland: Anolis punctatus-Cyrtosomum longicaudatum (97009), Os- waldocruzia vitti (97012, 97015, 97017), Oswaldofilaria brevicaudata (97011), Strongyluris oscari (97014, 97016, 97019), Falcaustra sp. (97010), Rhabdias sp. (97013, 97018); Anolis transversalis-Mesocestoides sp. (97022), Cyrtosomum longicaudatum (97023); Strongyluris oscari (97020, 97021, 97024). Anolis punctatus harbored six species of helminths; A. transversalis three (table 1). Of these, only two species, Cyrtosomum longicau- datum (in large intestines), and Strongyluris os- cari (in large and small intestines), occurred in both host species. Cyrtosomum longicaudatum © Koninklijke Brill NV, Leiden, 2006. Amphibia-Reptilia 27 (2006): 575-579 Also available online - www.brill.nl/amre

Accuracy of fetal lung volume assessed by three‐dimensional sonography

To determine the accuracy and precision of prenatal three-dimensional (3D) ultrasound in estimating fetal lung volume using the rotational multiplanar technique (VOCAL) by comparing it to postmortem volume measurements. Fetal lung volume was measured during 3D ultrasound examination using a rotational multiplanar technique in eight cases of congenital diaphragmatic hernia (CDH) (six left and two right-sided) and in 25 controls without pulmonary malformation, immediately before termination. Prenatal 3D sonographic estimates of fetal lung volume were compared with postmortem measurement of fetal lung volume achieved by water displacement. The intraclass correlation coefficient of fetal lung volume estimated by 3D ultrasound and measured at postmortem examination was 0.95 in CDH cases and 0.99 in controls. Based on Bland-Altman analysis, the bias, precision and limits of agreement were, respectively, 0.35 cm(3), 1.46 cm(3) and between -2.51 and + 3.21 cm(3) in cases with CDH and 0.08 cm(3), 2.80 cm(3) and between -5.41 and + 5.57 cm(3) in controls. The mean relative error of 3D ultrasound fetal lung volume measurement was -7.19% (from -42.70% to + 18.11%) in CDH cases and -0.72% (from -30.25% to + 19.22%) in controls, while the mean absolute error of 3D ultrasound fetal lung volume measurement was 1.40 (range, 0.71-2.52) cm(3) and 2.12 (range, 0.05-4.98) cm(3), respectively. Accuracy of 3D ultrasound for measuring fetal lung volumes was 84.86 (range, 57.30-99.48)% in cases with CDH and 91.38 (range, 69.75-99.45)% in controls. The mean intraobserver variability for lung volume estimated by 3D ultrasound was 0.28 cm(3) in controls and 0.17 cm(3) in CDH cases. Prenatal 3D ultrasound can estimate accurately fetal lung volume using the rotational multiplanar technique for volume measurements (VOCAL), even in fetuses with very small lungs, such as cases with isolated CDH.