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AIM: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS. METHODS: ARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (VT 20 m/kg body weight) until P/F ratio < 26.7 kPa. The animals were treated with two intratracheal boluses of 2.5 mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf®), both surfactants containing 80 mg phospholipids/mL, or air as control. The animals were subsequently ventilated (VT 8-9 m/kg body weight) for an additional 3 h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNFα IL-6 and IL-8 in lung homogenates were evaluated. RESULTS: Both surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1 h, P/F ratio and PaO2 at 1.5 h compared to rSP-C33Leu surfactant. CONCLUSION: This study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

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BACKGROUND: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy. METHODS: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated. RESULTS: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups. CONCLUSION: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury.

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BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-ß) in the lung epithelium. METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-ß pathway markers, regional histology, and cytokines were evaluated. RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-ß pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR. CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-ß pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

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The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices.

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Brachyspira hyodysenteriae, the aetiological agent of swine dysentery, and a recently proposed and closely related enteropathogenic spirochaete "Brachyspira suanatina", originally isolated from pigs or mallards (Anas platyrhynchos), were used to inoculate week-old mallard ducklings orally or cloacally. The colonization rate, clinical outcome, faecal dry matter content, blood leucocyte counts and gross, microscopical and electron microscopical features 14-16 days post-inoculation were investigated at necropsy examination. Strains of "B. suanatina" of pig and mallard origin and B. hyodysenteriae of mallard origin colonized the ducklings by oral inoculation, and colonization was also established by cloacal inoculation with a "B. suanatina" strain of mallard origin. The porcine reference strain of B. hyodysenteriae (B204) failed to colonize the birds. Unchallenged contact birds in one of the challenge groups were readily colonized by a strain of "B. suanatina" of mallard origin. The proportion of colonized birds differed significantly between the challenge groups (P < 0.0001). For each challenge group, the inoculum and a randomly selected subset of recovered isolates had an identical biochemical profile and banding pattern by randomly amplified polymorphic DNA (RAPD) analysis. None of the birds developed clinical signs of gastrointestinal disease during the trial. The faecal dry weight contents, body weights and total leucocyte and heterophil counts did not differ between the various groups of birds. At the microscopical and electron microscopical levels, the caecal mucosa in some of the Brachyspira culture-positive birds had sharply demarcated epithelial cell changes and there were features of irreversible cell damage in crypt necks coinciding with spirochaetal infiltration of the mucosa. The crypts in Brachyspira culture-positive birds were deeper than in culture-negative birds (median: 237 microm and 218 microm, respectively, P = 0.019). This challenge model was well suited for use in mallards and consistent with previous findings that strongly haemolytic Brachyspira spp. may cross the species barrier between pigs and birds.

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The relation between supraphysiologic circulating testosterone levels and prostatic diseases is unclear and difficult to study in men. Animal models may be advantageous. Based on a pilot study, testosterone enantate 50 mg (n=12) or 25 mg (n=12) was administered to guinea-pigs intramuscularly every 3 weeks, for either 7 or 14 months. The histopathology of the prostate was described. Epithelial hyperplasia was found in 14/21 animals receiving testosterone and in 7/12 very old animals, but no such changes were found in the sham or castrated animals. Testosterone stimulation seems to induce epithelial hyperplasia, but not cancer, in the guinea-pig prostate.

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To test the hypothesis that airborne microbial cell wall components could induce an inflammatory response in the lungs, measurements were made of the amounts of bacterial endotoxin and (1-->3)-beta-D-glucan in laboratory animal bedding materials. Groups of rats were exposed by inhalation to airborne endotoxin, (1-->3)-beta-D-glucan or a combination of the two for 5 weeks. The results demonstrated that measurable amounts of endotoxin and (1-->3)-beta-D-glucan could be detected in the different bedding materials. In contrast to animals at delivery, those kept on bedding for 5 weeks showed moderate inflammatory reactions in the lung. These were most pronounced among animals exposed to endotoxin and (1-->3)-beta-D-glucan. The results suggest that further studies need to be undertaken to elucidate the role of microbial cell wall products in the development of inflammatory lung responses among research animals.

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Brachyspira spp. were isolated from 21 of 32 sampled dogs (66%) in a colony of Swedish beagle dogs with a history of diarrhea and from 3 of 17 Swedish pet dogs (17%) with diarrhea. All Swedish isolates were weakly beta-hemolytic and gave a negative indole reaction. Eighty-eight percent showed negative alpha-galactosidase and hippurate reactions, but a positive beta-glucosidase reaction. Two isolates were hippurate positive with a negative beta-glucosidase reaction. One additional German isolate diverged by showing a positive indole reaction in combination with a positive hippurate reaction. Sequencing of 16S rDNA indicated that the hippurate-positive isolates belonged to the species Brachyspira pilosicoli. Four representative isolates were examined using pulsed-field gel electrophoresis (PFGE) and compared with six reference strains and five porcine isolates of Brachyspira spp. The canine isolates clustered together in the PFGE analysis. Necropsy examination of a culture-positive B. pilosicoli colony-raised beagle dog revealed macro- and microscopical lesions of colitis with numerous spiral-shaped bacteria in the lumens of the crypts, in goblet cells and within the colonic epithelium.

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Health practitioners use various models for facilitating health or lifestyle change, which entails either stopping an unhealthy behavior or promoting a new healthy behavior. Four models offer evidence-based, systematic, and integrative approaches to lifestyle change. They are: the Transtheoretical Model or Stages of Change; Brief Motivational Interviewing; Prevention Oriented Primary Care; and the ECBIS Psychotherapy Model (Emotion, Cognition, Behavioral, Interpersonal, and System). This article reviews each model and features a case illustration to demonstrate how these models can be integrated and applied clinically to help a patient change multiple health behaviors.

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The use of condoms as part of the prevention of unintended pregnancies and sexually transmitted diseases (STDs) in adolescents is evaluated in this policy statement. Sexual activity and pregnancies decreased slightly among adolescents in the 1990s, reversing trends that were present in the 1970s and 1980s, while condom use among adolescents increased significantly. These trends likely reflect initial success of primary and secondary prevention messages aimed at adolescents. Rates of acquisition of STDs and human immunodeficiency virus (HIV) among adolescents remain unacceptably high, highlighting the need for continued prevention efforts and reflecting the fact that improved condom use can decrease, but never eliminate, the risk of acquisition of STDs and HIV as well as unintended pregnancies. While many condom education and availability programs have been shown to have modest effects on condom use, there is no evidence that these programs contribute to increased sexual activity among adolescents. These trends highlight the progress that has been made and the large amount that still needs to be accomplished.

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Sexual assault is a broad-based term that encompasses a wide range of sexual victimizations, including rape. Since the American Academy of Pediatrics published its last policy statement on this topic in 1994, additional information and data have emerged about sexual assault and rape in adolescents, the adolescent's perception of sexual assault, and the treatment and management of the adolescent who has been a victim of sexual assault. This new information mandates an updated knowledge base for pediatricians who care for adolescent patients. This statement provides that update, focusing on sexual assault and rape in the adolescent population.

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An animal model for rhinogenic sinusitis was developed in rabbits naturally colonized with Bordetella bronchiseptica. It was found that ostial occlusion predisposes the sinus to invasion with this opportunistic bacterium and subsequent sinusitis as a result of reduced local host defense. In addition to the inflammatory lesions in the sinus, bronchitis and pneumonia were found in 84% of the experimental rabbits, suggesting that ostial dysfunction can also contribute to infectious disease of the lower respiratory tract. In such a model it is possible to study the significance of asymptomatic carriage of potential pathogens after ostial occlusion.

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This review was conducted to analyze the literature regarding the association between psychological depression and cardiovascular disease (CVD). The literature was reviewed through Medline and Psychlit. Articles were located using search terms such as depression, CVD, coronary artery disease, and cardiac risk factor. The search included articles from 1980 through 1999. Both the cross-sectional and prospective data suggest that psychological depression is a risk factor for and an aggravating factor of preexisting CVD. Proposed pathophysiologic mechanisms and therapeutic implications are discussed.

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We describe statistical techniques for effective evaluation of large virtual combinatorial libraries (> 10(10) potential compounds). The methods described are used for computationally evaluating templates (prioritization of candidate libraries for synthesis and screening) and for the design of individual combinatorial libraries (e.g., for a given diversity site, reagents can be selected based on the estimated frequency with which they appear in products that pass a computational filter). These statistical methods are powerful because they provide a simple way to estimate the properties of the overall library without explicitly enumerating all of the possible products. In addition, they are fast and simple, and the amount of sampling required to achieve a desired precision is calculable. In this article, we discuss the computational methods that allow random product selection from a combinatorial library and the statistics involved in estimating errors from quantities obtained from such samples. We then describe three examples: (1) an estimate of average molecular weight for the several billion possible products in a four-component Ugi reaction, a quantity that can be calculated exactly for comparison; (2) the prioritization of four templates for combinatorial synthesis using a computational filter based on four-point pharmacophores; and (3) selection of reagents for the four-component Ugi reaction based on their frequency of occurrence in products that pass a pharmacophore filter.

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The risks and negative consequences of adolescent sexual intercourse are of national concern, and promoting sexual abstinence is an important goal of the American Academy of Pediatrics. In previous publications, the American Academy of Pediatrics has addressed important issues of adolescent sexuality, pregnancy, sexually transmitted diseases, and contraception. The development of new contraceptive technologies mandates a revision of this policy statement, which provides the pediatrician with an updated review of adolescent sexuality and use of contraception by adolescents and presents current guidelines for counseling adolescents on sexual activity and contraceptive methods.

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The purpose of this study was to demonstrate that a simple submaximal "step-test" could be used as an exercise challenge to identify elementary school students with suspected but undiagnosed asthma. This article also describes a protocol for exercise testing that can be used in epidemiological evaluations. School age children grades 1-4 with suspected but undiagnosed asthma were identified by a 12-item questionnaire completed by a parent or guardian. Only students identified with suspected asthma by questionnaire were exercise challenged on a step-test it baseline spirometry was normal and there was no contraindication for intense aerobic activity. Possible asthma was defined as a 15% or greater decrease in FEV1 or a 25% or greater decrease in FEF25-75 from baseline at either 3 or 10 minutes. The exercise protocol included spirometry before and after stepping continuously for 5 minutes at an exercise intensity sufficient to maintain a heart rate between 150 and 200 beats per minute. Heart rate was continuously monitored throughout the exercise period. Testing was completed at school. No complications occurred during the exercise testing. Exercise testing was completed on 548 students with suspected undiagnosed asthma. Thirty students (6%) had exercise test changes in pulmonary function that met established criteria for suspecting asthma. A board-certified pediatric allergist/immunologist or private physician examined 26 of the 30 students with positive exercise testing. Asthma was diagnosed in 23 (88.89%) of these students. All students with impaired pulmonary function after exercise were able to return to class after a short period of observation. In conclusion, a simple, reproducible school-based exercise protocol can be used to identify students with suspected undiagnosed asthma.

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Lymphoscintigraphy is a sensitive, inexpensive, relatively noninvasive method of identifying lymphatic drainage patterns and sentinel lymph nodes in patients with malignant melanoma. Lymphoscintigraphy with filtered technetium-99m sulfur colloid allows prompt visualization of the lymphatic system, produces high-quality images, and delivers a low radiation dose to the patient. In addition, good regional lymph node retention is seen with filtered Tc-99m sulfur colloid, improving the success rate of intraoperative gamma probe localization. In combination with surgical localization, lymphoscintigraphy allows preoperative and intraoperative identification of the sentinel node in patients with intermediate thickness melanomatous lesions, obviating radical lymph node dissection in most patients and possibly prolonging their survival. Variables such as tumor location, type and preparation of radiopharmaceutical, injection technique, imaging technique, and prior surgical intervention influence the efficacy of lymphoscintigraphy. Nevertheless, lymphoscintigraphy is recommended as a cost-effective preoperative procedure in all patients planning to undergo elective lymph node dissection. Because of the unpredictability of lymphatic drainage, preoperative scintigraphic findings may lead to changes in surgical management.

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