Successful deprescribing of proton pump inhibitors with a patient-centered process: the DESPIBP Project.

BACKGROUND: Proton-pump inhibitors (PPIs) are among the most frequently prescribed drugs, but they are being overprescribed. OBJECTIVE: To evaluate the applicability of a deprescription algorithm in hospitalized patients with chronic PPI use. METHODS: A prospective study including consecutive gastroenterology department hospitalized patients with chronic PPI use. The prescription was reassessed and a deprescribing algorithm was applied. Follow-up was carried out at 4, 12, and 24 weeks. RESULTS: A total of 513 (44.22%) of 1160 had chronic PPI use; 371 met inclusion criteria and were evaluated: 285 (76.82%) with appropriate prescription and 86 (23.18%) with inappropriate, mainly (52.30%) due to polypharmacy. Seventy-five patients accepted the deprescribing process. Sixty-one (81.33%) maintained deprescription at week 4, 56 (74.66%) at week 12, and 54 (72.00%) at week 24. Eleven of 21 restarted the PPI because of symptoms. No differences were found between the successful deprescription group and the unsuccessful one, regarding sex (p = 0.877), age (p = 0.635), PPI indication (p = 0.663), or deprescription regimen (p = 0.805). No patient had any adverse event attributable to deprescription. CONCLUSION: There is a high inappropriate indication for PPIs in patients admitted to the gastroenterology department. The application of a patient-centered deprescribing algorithm is a safe and effective strategy to reduce their inappropriate consumption in the medium term.

Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-ß3 null mutant mice.

BACKGROUND: Cleft palate (CP) constitutes the most frequently seen orofacial cleft and is often associated with low folate status. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis, repair, and methylation. Whether the administration of isolated folic acid (FA) supplements prevents the CP caused by genetic mutations is unknown, as is its effect on the mechanisms leading to palate fusion. METHODS: FA was administered to females from two different strains of transforming growth factor ß3 heterozygous mice. Null mutant progeny of these mice exhibit CP in 100% of cases of varying severity. We measured cleft length, height of palatal shelf adhesion, and the number of proliferating mesenchymal cells. Immunohistochemistry was also carried for collagen IV, laminin, fibronectin, cytokeratin-17, and EGF. RESULTS: FA supplementation significantly reduced CP severity and improved palatal shelf adhesion in both strains both in vivo and in vitro. Medial edge epithelium proliferation increased, and its differentiation was normalized as indicated by the presence and disposition of collagen IV, laminin, fibronectin, and cytokeratin-17. CONCLUSIONS: A maternal FA supplementation reduces the CP appearance by improving the mechanisms leading to palatal shelf adhesion.

Reduction in mortality associated with secondary cytomegalovirus prophylaxis after solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. The role of secondary CMV prophylaxis in this population remains unclear. METHODS: Retrospective cohort study in a single center. SOT recipients treated for CMV infection from 2007 to 2014 were studied to determine the efficacy and safety of secondary prophylaxis and its impact on graft loss and mortality. The outcome variable was CMV replication in the first 3 months after the end of therapy. Secondary variables were crude mortality and graft lost censored at 5 years after transplantation. Propensity score for the use of secondary prophylaxis was used to control selection bias. RESULTS: Of the 126 treated patients, 103 (83.1%) received CMV secondary prophylaxis. CMV relapse occurred in 44 (35.5%) patients. The use of secondary prophylaxis was not associated with fewer relapses (34.0% in patients with prophylaxis vs 42.9% in those without prophylaxis, P = .29). After a mean follow-up of 32.1 months, graft loss was not different between both groups but patient mortality was significantly lower in patients who received secondary prophylaxis (5.8% vs 28.6%, P = .003). CONCLUSION: Secondary prophylaxis did not prevent CMV infection relapse but it was associated with improved patient survival.

X-ray micro-computed tomography of postmortem brain tissue using potassium dichromate as a contrast agent.

No abstract available.

[Pulmonary lobectomy in children: the sooner the better?] / Lobectomía pulmonar en niños: ¿cuanto antes mejor?

AIM OF THE STUDY: Recommendation of early pulmonary resection in asymptomatic congenital pulmonary airway malformations (CPAMs) is based on the presumed compensatory lung growth during the first months of life. Our aim is to analyze the long-term pulmonary function after lobectomy before and after one year of age using spirometry. METHODS: We performed a retrospective review of children who underwent pulmonary lobectomy for CPAM between 2001 and 2016. Patients who were old enough (>5 years) to carry out a spirometry were included in the study and were divided into 2 groups (surgery before or after 12 months of age). Pulmonary function testing values were considered normal if they were >80% of predicted. MAIN RESULTS: Forty-seven patients underwent pulmonary lobectomy for CPAM, 23 of them met the inclusion criteria and prospectively performed a spirometry. Among them, 7 had surgery before and 16 after one year of age (0.1 vs. 2); being both groups comparable in terms of sex, type of CPAM and surgical approach. Time from surgery until pulmonary function testing was longer in patients who had surgery before one year of age (9.1 vs. 4.6 years, p = 0.003). After correcting results by time from surgery until spirometry, a better FEV1/FVC was found in patients who had surgery after one year of age (90% vs. 77%, p = 0.043). CONCLUSION: Although spirometry may be influenced by many other variables, these preliminary results do not support the current recommendation of performing early lobectomy in CPAMs. Further studies are required in order to resolve the best age to perform pulmonary lobectomy.

INTRODUCCION/OBJETIVO: La resección temprana de las malformaciones pulmonares asintomáticas ofrece el beneficio teórico de optimizar el crecimiento pulmonar compensatorio durante la infancia. El objetivo de este estudio es determinar si la lobectomía antes del año de vida se asocia con mejor función pulmonar a largo plazo. MATERIALES Y METODOS: Revisión de pacientes en los que se realizó lobectomía pulmonar desde 2001, incluyendo los que tenían edad suficiente para realizar una espirometría (>5 años). Fueron divididos en dos grupos: lobectomía antes o después de 12 meses de vida. Los parámetros espirométricos se consideraron normales cuando eran mayores del 80% esperado. RESULTADOS: Veintitrés de los 47 pacientes intervenidos cumplieron los criterios de inclusión. Siete fueron intervenidos antes (0,1 ± 0,4 años) y 16 después del año de vida (2 ± 3,6 años), siendo ambos grupos comparables en sexo, tipo de malformación y abordaje quirúrgico. El tiempo de seguimiento desde la cirugía hasta que se realizó la espirometría fue mayor en los pacientes intervenidos antes del año de vida (9,1 vs. 4,6 años, p = 0,003). Tras corregir los resultados por el tiempo de seguimiento, se objetivó un mejor cociente FEV1/FVC en los pacientes intervenidos después del año de vida (90% vs. 77%, p = 0,043). CONCLUSION: Aunque la espirometría puede estar influenciada por otras variables, los datos de nuestro estudio no apoyan la recomendación actual de realizar resección temprana en las malformaciones pulmonares congénitas asintomáticas. Se necesitan estudios prospectivos con mayor número de pacientes para determinar la mejor edad para realizar la lobectomía.

[Long-term results of the early endoscopic treatment of acquired tracheal-subglottic stenosis: 10 years of experience]. / Resultados a largo plazo del tratamiento endoscópico precoz de las estenosis subglóticas y traqueales adquiridas: 10 años de experiencia.

INTRODUCTION: Acquired stenosis of the airway is a common complication after endotracheal intubation. Endoscopic dilation has been accepted as the treatment of choice in cases detected precociously. Our goal is to know the current status of the patients treated in our hospital with endoscopic dilation in the last 10 years. MATERIAL AND METHODS: Retrospective cohort study of patients with subglottic and tracheal acquired stenosis (STAS) early treated endoscopically with balloon dilation at our center in the last 10 years. Bronchoscopy control at 2 weeks, a month, 3 and 6 months post-dilation were performed and later on depending on the symptoms. RESULTS: 32 patient were treated in the period considered. The median age was 4.5 (3-120) months. There were necessary 2.5 (1-5) dilations per patient. All cases were extubated in the operating room or in the following 24 hours. There were no complications during the procedure. Follow-up time was 6 (1-10) years. Only 1 of the 32 patients have had recurrence of stenosis 2 years after, it was secondary to reintubations due to new surgical interventions; which it was dilated successfully. CONCLUSIONS: Early endoscopic dilation in the acquired airway stenosis is a safe and effective long-term procedure. The results support the use of this technique as a treatment of choice in these patients.

INTRODUCCION: La estenosis adquirida de la vía aérea es una complicación frecuente tras la intubación endotraqueal. La dilatación endoscópica ha sido aceptada como tratamiento de elección en los casos detectados de forma precoz. Nuestro objetivo es conocer el estado actual de los pacientes tratados en nuestro centro mediante dilatación endoscópica en los últimos 10 años. MATERIAL Y METODOS: Estudio de cohorte retrospectivo de pacientes con estenosis subglóticas y traqueales adquiridas (ESTA) tratadas endoscópicamente mediante dilatación con balón en nuestro centro en los últimos 10 años. Se realizaron broncoscopias de control a las 2 semanas, al mes, a los 3 y 6 meses postdilatación y posteriormente en función de la clínica. RESULTADOS: Se trataron 32 pacientes de ESTA de reciente aparición en dicho periodo. La mediana de edad fue de 4,5 (3-120) meses. Fueron necesarias 2,5 (1-5) dilataciones por paciente. Todos los pacientes fueron extubados en quirófano o en las 24 horas siguientes al procedimiento. No hubo complicaciones durante los procedimientos ni durante el postoperatorio. El tiempo de seguimiento fue de 6 (1-10) años. Solo 1 de los 32 pacientes presentó recidiva de la estenosis 2 años después que fue secundaria a reintubaciones por nuevas intervenciones quirúrgicas; la cual se dilató nuevamente. CONCLUSIONES: La dilatación endoscópica precoz en las estenosis adquiridas de la vía aérea es un procedimiento seguro y eficaz a largo plazo. Los resultados avalan el uso de esta técnica como tratamiento de elección en estos pacientes.

High incidence of FXI deficiency in a Spanish town caused by 11 different mutations and the first duplication of F11: Results from the Yecla study.

INTRODUCTION: Factor XI (FXI) deficiency is a rare disorder with molecular heterogeneity in Caucasians but relatively frequent and molecularly homogeneous in certain populations. AIM: To characterize FXI deficiency in a Spanish town of 60 000 inhabitants. METHODS: A total of 324 764 APTT tests were screened during 20 years. FXI was evaluated by FXI:C and by Western blot. Genetic analysis of F11 was performed by sequencing, multiplex ligation-dependent probe amplification and genotyping. RESULTS: Our study identified 46 unrelated cases and 170 relatives with FXI deficiency carrying 12 different genetic defects. p.Cys56Arg, described as founder mutation in the French-Basque population, was identified in 109 subjects from 24 unrelated families. This mutation was also identified in 2% of the general population. p.Cys416Tyr, c.1693G>A and p.Pro538Leu were identified in 7, 6 and 2 unrelated families, respectively. NGS analysis of the whole F11 gene revealed a common haplotype for each of the four recurrent mutations, suggesting a founder effect. The analysis of plasma FXI of four p.Pro538Leu homozygous carriers revealed that this variant was not activated by FXIIa. We identified four mutations previously described in other Caucasian subjects with FXI deficiency (p.Lys536Asn; p.Thr322Ile, p.Arg268Cys and c.325G>A) and four new gene defects: p.(Cys599Tyr) potentially causing a functional deficiency, p.(Ile426Thr), p.(Ile592Thr) and the first worldwide duplication of 1653 bp involving exons 8 and 9. Bleeding was rare and mild. CONCLUSIONS: Our population-cohort study supplies new evidences that FXI deficiency in Caucasians is more common than previously thought and confirmed the wide underlying genetic heterogeneity, caused by both recurrent and sporadic mutations.

Effect of detomidine or romifidine constant rate infusion on plasma lactate concentration and inhalant requirements during isoflurane anaesthesia in horses.

OBJECTIVE: Influence of detomidine or romifidine constant rate infusion (CRI) on plasma lactate concentration and isoflurane requirements in horses undergoing elective surgery. STUDY DESIGN: Prospective, randomised, blinded, clinical trial. ANIMALS: A total of 24 adult healthy horses. METHODS: All horses were administered intramuscular acepromazine (0.02 mg kg-1) and either intravenous detomidine (0.02 mg kg-1) (group D), romifidine (0.08 mg kg-1) (group R) or xylazine (1.0 mg kg-1) (group C) prior to anaesthesia. Group D was administered detomidine CRI (10 µg kg-1 hour-1) in lactated Ringer's solution (LRS), group R romifidine CRI (40 µg kg-1 hour-1) in LRS and group C an equivalent amount of LRS intraoperatively. Anaesthesia was induced with ketamine and diazepam and maintained with isoflurane in oxygen. Plasma lactate samples were taken prior to anaesthesia (baseline), intraoperatively (three samples at 30 minute intervals) and in recovery (at 10 minutes, once standing and 3 hours after end of anaesthesia). End-tidal isoflurane percentage (Fe'Iso) was analysed by allocating values into three periods: Prep (15 minutes after the start anaesthesia-start surgery); Surgery 1 (start surgery-30 minutes later); and Surgery 2 (end Surgery 1-end anaesthesia). A linear mixed model was used to analyse the data. A value of p<0.05 was considered significant. RESULTS: There was a difference in plasma lactate between 'baseline' and 'once standing' in all three groups (p<0.01); values did not differ significantly between groups. In groups D and R, Fe'Iso decreased significantly by 18% (to 1.03%) and by 15% (to 1.07%), respectively, during Surgery 2 compared with group C (1.26%); p<0.006, p<0.02, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intraoperative detomidine or romifidine CRI in horses did not result in a clinically significant increase in plasma lactate compared with control group. Detomidine and romifidine infusions decreased isoflurane requirements during surgery.

Structure and reorientational dynamics of 1-F-adamantane.

The polymorphism and the dynamics of a simple rigid molecule (1-fluoro-adamantane) have been studied by means of X-ray powder diffraction and broadband dielectric spectroscopy. At temperatures below the melting point, the molecule forms an orientationally disordered Phase I with a cubic-centered structure (Phase I, Fm3¯m, Z = 4). This phase possesses eight equilibrium positions for the fluorine atom, with equal occupancy factors of 1/8. A solid-solid phase transition to a low-temperature tetragonal phase (Phase II, P4¯2(1)c, Z = 2) reduces the statistical disorder to only four possible equivalent sites for the fluorine atom, with fractional occupancies of 1/4. The dynamics has been rationalized under the constraints imposed by the space group of the crystal structure determined by powder X-ray diffraction. The dielectric spectroscopy study reveals that the statistical disorder in Phase II is dynamic in character and is associated with reorientational jumps along the two- and three-fold axes. In the dielectric loss spectra, the cooperative (α) relaxation exhibits a shoulder on the high-frequency side. This remarkable finding clearly reveals the existence of two intrinsic reorientational processes associated with the exchange of the F atom along the four sites. In addition to such "bimodal" relaxation, a secondary Johari-Goldstein relaxation is detected at lower temperatures.

Epidermal growth factor impairs palatal shelf adhesion and fusion in the Tgf-ß 3 null mutant.

The cleft palate presented by transforming growth factor-ß3 (Tgf-ß3) null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-ß1 (Tgf-ß1) and muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in Tgf-ß3 knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, Tgf-ß1 and Msx-1 in Tgf-ß3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-ß3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal mesenchyme. Inhibition of TGF-ß1 does not affect either EGF or Msx-1 expression.

Animal board invited review: Improving animal health and welfare in the transition of livestock farming systems: Towards social acceptability and sustainability.

The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasises the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analysing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers' willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organisation of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

Skin test-positive immediate hypersensitivity reaction to iodinated contrast media: the role of controlled challenge testing.

BACKGROUND: Immediate hypersensitivity reactions (IHR) to iodinated contrast media (ICM) have traditionally been considered nonallergic; however, the increasingly frequent reporting of positive skin test and basophil activation test results suggests a specific allergic mechanism in some patients. Skin tests have been proposed as a useful tool for diagnosis, although their sensitivity and predictive values remain to be determined. The role of controlled challenge testing has not been assessed. OBJECTIVE: We aimed to evaluate the role of controlled challenge testing in skin test-positive IHR to ICM. PATIENTS AND METHODS: We evaluated 106 patients with IHR to ICM by performing skin tests with the agent that caused the reaction. Patients with a positive result were selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent controlled challenge test with an alternative skin test-negative ICM; a further 2 patients underwent computed tomography with an alternative skin test-negative ICM. No premedication was administered. RESULTS: Intradermal test results were positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%). Five of the 11 patients tolerated a controlled challenge test with an alternative skin test-negative ICM. The 2 patients who underwent computed tomography with an alternative skin test-negative ICM tolerated the medium. CONCLUSIONS: Skin tests are useful for the diagnostic workup in patients with an allergic IHR to ICM. Since ICM cannot be avoided in many patients because they are irreplaceable in some diagnostic or therapeutic techniques, an alternative safe ICM should be investigated for future procedures. We propose the use of controlled challenge tests based on skin test results to address this need in skin test-positive reactions in order to identify an alternative non-cross-reactive ICM.

An unexpected high-pressure stability domain for a lower density polymorph of benzophenone.

For over a century, it was thought that the crystalline polymorph II of benzophenone does not possess a stable domain in the pressure-temperature phase diagram. With a combination of new experimental results and literature data, this case of crystalline dimorphism has finally been solved and it is shown that form II possesses a stable domain at high pressure and high temperature, even though its density is lower than that of form I, the stable form under ordinary pressure and temperature conditions. The phase diagram of benzophenone is a clear demonstration of the fact that to understand the phase behaviour of a chemical substance both the exchange of heat (due to the change in intermolecular interactions) and work (due to the change of volume at a given pressure) need to be taken into account.

SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

Use of ultrasound in the reproductive management of dairy cattle.

The significant decrease in fertility observed in dairy cattle during the last few decades and increasing requirements by the farmers have made a regular control of reproduction indispensable to urgently identify and solve potential problems affecting reproductive efficiency. Traditionally, the main diagnostic methods used for reproductive control in cattle included rectal palpation, inspection of vaginal discharge and vaginoscopy. Since the 1990 s, the use of ultrasound (US) has become a common diagnostic method as a result of the new advances made in the development of US scans: smaller size, high level of autonomy, high image quality and accessible prices. Ultrasound improves accuracy in the diagnoses of stages of the oestrous cycle, ovarian and uterine pathologies, and pregnancy diagnosis. In addition, it facilitates the diagnosis of alterations during pregnancy (embryo mortality, foetal malformations, etc.) and helps determining foetal sex from day 55 of pregnancy.

Effects of two alveolar recruitment manoeuvres (sustained inflation and stepwise) followed by positive end-expiratory pressure on cardiac output (measured with lithium dilution), invasive blood pressure and arterial oxygen tension in isoflurane-anaesthetised goats.

Alveolar recruitment manoeuvres (ARM) performed during general anaesthesia improve oxygenation; however cardiovascular depression may be observed. The aim of the study was to compare the effects of sustained inflation (SI) and stepwise ARMs on cardiac output (CO), mean arterial blood pressure and arterial oxygen tension (PaO2) in ten mechanically ventilated goats anaesthetised with isoflurane. In the SI ARM, peak inspiratory presure (PIP) was increased to 30 cmH2O and sustained for 20 s. In the stepwise ARM, the PIP was increased by 5 cmH2O each minute for three minutes from 10 to 25 cmH2O. Both ARMs were followed by positive end-expiratory pressure of 5 cmH2O. Paired lithium dilution CO measurements and arterial blood samples were obtained before and after each ARM. The order of the ARM was randomised and each goat was subjected to both techniques. Data was reported as median and interquartile range (IQR). Significance was set at 0.05. The median change in CO (measured by subtracting values after and before ARM) was -0.15 L min-1 (IQR -0.51; 0.03) and - 0.90 L min-1 (IQR -1.69; -0.58) for SI and stepwise ARM respectively (p = 0.04). The median change in PaO2 was 3 kPa (IQR -2.7; 7.6) and 0.4 kPa (IQR -3.4; 5.5) for SI and stepwise ARM respectively (p = 0.03). In conclusion, SI ARM causes less impact on CO and provides a better improvement in PaO2 compared to stepwise ARM in goats.

On the dimorphism of prednisolone: The topological pressure-temperature phase diagram involving forms I and II.

The dimorphism of the corticosteroid anti-inflammatory drug prednisolone has been investigated by the construction of a topological pressure-temperature phase diagram, using crystallographic and calorimetric data. The system is enantiotropic, because the temperature of the I-II equilibrium under atmospheric conditions (400-463 K) is lower than that of the two melting equilibria (518.7 K for form II and 526.3 K for form I). The slope of the I-II equilibrium in the pressure-temperature phase diagram is negative and relatively steep; therefore, form II, which is the stable form at room temperature, will not easily encounter conditions where form I will become stable even under industrial processing conditions. On the other hand, extreme small amounts of form I have been observed to spontaneously transform into form II in a time interval of about six years at room temperature and it can be concluded that although form I is very persistent under ambient conditions, it does slowly convert into form II. Moreover, the system does not obey the density rule.