Carbapenem alternatives for treatment of bloodstream infections due to AmpC producing enterobacterales.

INTRODUCTION: Carbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated. METHODS: We conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed. RESULTS: Seventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999). CONCLUSIONS: Targeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

Gastrointestinal colonization by OXA-48-producing Enterobacterales: risk factors for persistent carriage.

Carbapenem-resistant Enterobacterales (CRE) infections are a major health problem. Intestinal colonization is a key factor in developing infection. However, factors associated with persistent colonization by CRE are unknown. The aim of the study was to identify factors associated with persistent CRE gut colonization. This is a retrospective, single-centre, observational study of adult patients with CRE gut colonization between January 2015 and January 2020. Epidemiologic characteristics, comorbidities, infectious events, duration of hospitalization and antimicrobial treatment received in the follow-up period were collected. Colonization was defined as isolation in at least 2 rectal swab culture samples of CRE. Decolonization was defined as 3 negative rectal swab cultures or 2 negative cultures and a negative molecular test. A cohort of 86 patients with CRE gut colonization was selected: 44 patients with spontaneous decolonization (DC) and 42 patients with persistent colonization (PC). The mean follow-up period was 24 months (IQR 14-33) in the DC group vs. 25 months (IQR 16-36) in the PC group (p = 0.478). Patient characteristics were similar between both groups. Colonization by other MDR microorganisms was high (44 patients, 51%) and slightly more common in the PC group (PC 60% vs. DC 43%, p = 0.139). The use of ceftazidime-avibactam was more common among the PC group (PC 33% vs. DC 14%, p = 0.041). We observed a higher percentage of antimicrobial therapy in the previous 30 days (PC 68% vs. DC 57%, p = 0.371) and 90 days (PC 81% vs. DC 82%, p = 0.353) in the PC group. Multivariable analysis showed that patients that have received ceftazidime-avibactam therapy (OR 4.9 95% CI [1.45-16.39], p = 0.010), and those colonized by other MDR microorganisms (OR 2.5, 95% CI [0.96-6.25], p = 0.060) presented a higher risk of PC. Ceftazidime-avibactam use and colonization by other MDR microorganisms might be associated with CRE persistent gut colonization.

Ceftazidime-avibactam treatment in bacteremia caused by OXA-48 carbapenemase-producing Klebsiella pneumoniae.

Therapeutic options for bacteremia caused by carbapenem-resistant Enterobacterales (CRE) OXA-48-type are limited. The objective of this study was to analyze clinical success of CAZ-AVI compared with best available therapy (BAT) in patients with Klebsiella pneumoniae carbapenemase-producing OXA-48-type bacteremia (CRKp-OXA-48). We conducted a retrospective, single-center observational study in adult patients with CRKp-OXA-48 between December 2015 and May 2019. We collected the patients' clinical and epidemiological characteristics, antibiotic treatment (CAZ-AVI vs. BAT), and evolution. Factors associated with clinical success were analyzed using binary logistic regression. The study included 76 patients with CRKp-OXA-48-type bacteremia 33 received CAZ-AVI and 43 BAT. CAZ-AVI was mainly used in monotherapy (91%). Clinical success was more common in patients < 70-year-old (OR 4.79, 95% CI [1.435-16.002], p = 0.011) and CAZ-AVI treatment (OR 6.69, 95% CI [1.68-26.604], p = 0.007). Kaplan-Meier survival curve of 14-day mortality showed a lower mortality in patients who received CAZ-AVI (log rank 0.013). However, CAZ-AVI did not achieve statistical difference in IPTW for 14- and 30-day mortality (aOR 0.1, 95% CI [0.02-1.22], p = 0.076 and aOR 1.7, 95% CI [0.48-5.98], p = 0.413, respectively). CAZ-AVI treatment might be associated with a greater clinical success in CRKp-OXA-48 bacteremia.

The chloroplast genome of the hexaploid Spartina maritima (Poaceae, Chloridoideae): Comparative analyses and molecular dating.

The history of many plant lineages is complicated by reticulate evolution with cases of hybridization often followed by genome duplication (allopolyploidy). In such a context, the inference of phylogenetic relationships and biogeographic scenarios based on molecular data is easier using haploid markers like chloroplast genome sequences. Hybridization and polyploidization occurred recurrently in the genus Spartina (Poaceae, Chloridoideae), as illustrated by the recent formation of the invasive allododecaploid S. anglica during the 19th century in Europe. Until now, only a few plastid markers were available to explore the history of this genus and their low variability limited the resolution of species relationships. We sequenced the complete chloroplast genome (plastome) of S. maritima, the native European parent of S. anglica, and compared it to the plastomes of other Poaceae. Our analysis revealed the presence of fast-evolving regions of potential taxonomic, phylogeographic and phylogenetic utility at various levels within the Poaceae family. Using secondary calibrations, we show that the tetraploid and hexaploid lineages of Spartina diverged 6-10 my ago, and that the two parents of the invasive allopolyploid S. anglica separated 2-4 my ago via long distance dispersal of the ancestor of S. maritima over the Atlantic Ocean. Finally, we discuss the meaning of divergence times between chloroplast genomes in the context of reticulate evolution.

atz gene expressions during atrazine degradation in the soil drilosphere.

One of the various ecosystemic services sustained by soil is pollutant degradation mediated by adapted soil bacteria. The pathways of atrazine biodegradation have been elucidated but in situ expression of the genes involved in atrazine degradation has yet to be demonstrated in soil. Expression of the atzA and atzD genes involved in atrazine dechlorination and s-triazine ring cleavage, respectively, was investigated during in situ degradation of atrazine in the soil drilosphere and bulked samples from two agricultural soils that differed in their ability to mineralize atrazine. Interestingly, expression of the atzA gene, although present in both soils, was not detected. Atrazine mineralization was greatest in Epoisses soil, where a larger pool of atzD mRNA was consistently measured 7 days after atrazine treatment, compared with Vezin soil (146 vs. 49 mRNA per 10(6)16S rRNA, respectively). Expression of the atzD gene varied along the degradation time course and was profoundly modified in soil bioturbated by earthworms. The atzD mRNA pool was the highest in the soil drilosphere (casts and burrow-linings) and it was significantly different in burrow-linings compared with bulk soil (e.g. 363 vs. 146 mRNA per 10(6)16S rRNA, 7 days after atrazine treatment in Epoisses soil). Thus, consistent differences in atrazine mineralization were demonstrated between the soil drilosphere and bulk soil. However, the impact of bioturbation on atrazine mineralization depended on soil type. Mineralization was enhanced in casts, compared with bulk soil, from Epoisses soil but in burrow-linings from Vezin soil. This study is the first to report the effects of soil bioturbation by earthworms on s-triazine ring cleavage and its spatial variability in soil.

Ventromedial medullary pathway mediating cardiac responses evoked from periaqueductal gray.

Periaqueductal gray (PAG) is a midbrain region that projects to areas controlling behavioral and autonomic outputs and is involved in the behavioral and physiological components of defense reactions. Since Raphe Pallidus (RPa) is a medial medullary region comprising sympathetic premotor neurons governing heart function, it is worth considering the PAG-RPa path. We assessed: i) whether PAG projects to RPa; ii) the amplitude of cardiac responses evoked from PAG; iii) whether cardiovascular responses evoked from PAG rely on RPa. Experiments conducted in Wistar rats (±300 g) were approved by Ethics Committee CEUA-UFG (092/18). Firstly, (n = 3), monosynaptic retrograde tracer Retrobeads was injected into RPa; PAG slices were analyzed. Other two groups (n = 6 each) were anesthetized with urethane (1.4 g/kg) and chloralose (120 mg/kg) and underwent craniotomy, tracheostomy, catheterization of femoral artery and vein and of cardiac left ventricle. In one group, we injected the GABAA receptor antagonist, bicuculline methiodide (BMI - 40 pmol/100 nL) into lateral/dorsolateral PAG. Another group was injected (100 nL) with the GABAA receptor agonist muscimol (20 mM) into RPa, 20 min before BMI into PAG. The results were: i) retrogradely labelled neurons were found in PAG; ii) PAG activation by BMI caused positive chronotropism and inotropism, which were accompanied by afterload increases; iii) RPa inhibition with Muscimol reduced heart rate, arterial and ventricular pressures; iv) the subsequent PAG activation still increased arterial pressure, cardiac chronotropy and inotropy, but these responses were significantly attenuated. In conclusion, PAG activation increases cardiac chronotropy and inotropy, and these responses seem to rely on a direct pathway reaching ventromedial medullary RPa neurons.

Electronic band effects on the spin disorder resistivity of Gd(4)(Co(1-x)Cu(x))(3) compounds.

We present a study of the spin disorder resistivity ([Formula: see text]) and the electronic specific heat coefficient (γ) in Gd(4)(Co(1-x)Cu(x))(3) compounds, with x = 0.00, 0.05, 0.10, 0.20 and 0.30. The experimental results show a strongly nonlinear dependence of [Formula: see text] on the average de Gennes factor (G(av)) which, in similar intermetallic compounds, is usually attributed to the existence of spin fluctuations on the Co 3d bands. Values of γ were found around 110 mJ mol(-1) K(-2) for the Gd(4)(Co(1-x)Cu(x))(3) compounds, much larger than 38.4 mJ mol(-1) K(-2) found for the isostructural nonmagnetic Y(4)Co(3) compound. Using a novel type of analysis we show that the ratio [Formula: see text] follows a well-defined linear dependence on G(av), which is expected when appropriate dependencies with the effective electron mass are taken into account. This indicates that band structure effects, rather than spin fluctuations, could be the main cause for the strong electron scattering and γ enhancement observed in the Gd(4)(Co(1-x)Cu(x))(3) compounds. A discussion on relevant features of magnetization and electrical resistivity data, for the same series of compounds, is also presented.

RNA sequencing and analysis of three Lupinus nodulomes provide new insights into specific host-symbiont relationships with compatible and incompatible Bradyrhizobium strains.

Nitrogen fixation in the legume root-nodule symbiosis has a critical importance in natural and agricultural ecosystems and depends on the proper choice of the symbiotic partners. However, the genetic determinism of symbiotic specificity remains unclear. To study this process, we inoculated three Lupinus species (L. albus, L. luteus, L. mariae-josephae), belonging to the under-investigated tribe of Genistoids, with two Bradyrhizobium strains (B. japonicum, B. valentinum) presenting contrasted degrees of symbiotic specificity depending on the host. We produced the first transcriptomes (RNA-Seq) from lupine nodules in a context of symbiotic specificity. For each lupine species, we compared gene expression between functional and non-functional interactions and determined differentially expressed (DE) genes. This revealed that L. luteus and L. mariae-josephae (nodulated by only one of the Bradyrhizobium strains) specific nodulomes were richest in DE genes than L. albus (nodulation with both microsymbionts, but non-functional with B. valentinum) and share a higher number of these genes between them than with L. albus. In addition, a functional analysis of DE genes highlighted the central role of the genetic pathways controlling infection and nodule organogenesis, hormones, secondary, carbon and nitrogen metabolisms, as well as the implication of plant defence in response to compatible or incompatible Bradyrhizobium strains.

Superconducting and magnetic behaviour of niobium doped RuSr(2)Gd(1.5)Ce(0.5)Cu(2)O(10-δ).

Polycrystalline samples of Ru(1-x)Nb(x)Sr(2)Gd(1.5)Ce(0.5)Cu(2)O(10-δ), 0≤x≤0.5, have been synthesized and structurally characterized by x-ray diffraction (XRD). Resistivity, magnetization and AC susceptibility measurements have been done and analysed considering a phase separation scenario. A strong suppression of the cluster glass (CG) transition associated with niobium doping was identified. In fact, the CG phase was not present in samples for x≥0.2, leading to changes in the magnetic hysteresis loops measured at low temperatures. These hysteresis loops can be explained as a result of the contribution of two distinct magnetic phases: the canted AFM phase and embedded Ru(4+)-rich clusters which order as a CG in low temperatures. Interestingly, the significant changes in the magnetic response of the material do affect the superconducting transition temperature T(c). It was found that both T(c) and the superconducting fraction are reduced in samples which present the spin glass phase. Therefore, our results point to some coupling between magnetism and superconductivity in this ruthenocuprate family, the presence of the magnetic moment being deleterious for the superconductivity.

Superconducting Properties in Arrays of Nanostructured ß-Gallium.

Samples of nanostructured ß-Ga wires were synthesized by a novel method of metallic-flux nanonucleation. Several superconducting properties were observed, revealing the stabilization of a weak-coupling type-II-like superconductor ([Formula: see text] [Formula: see text] 6.2 K) with a Ginzburg-Landau parameter [Formula: see text] = 1.18. This contrasts the type-I superconductivity observed for the majority of Ga phases, including small spheres of ß-Ga with diameters near 15 µm. Remarkably, our magnetization curves reveal a crossover field [Formula: see text], where we propose that the Abrikosov vortices are exactly touching their neighbors inside the Ga nanowires. A phenomenological model is proposed to explain this result by assuming that only a single row of vortices is allowed inside a nanowire under perpendicular applied field, with an appreciable depletion of Cooper pair density at the nanowire edges. These results are expected to shed light on the growing area of superconductivity in nanostructured materials.

Efetividade do sistema de triagem em serviço de emergência privado: estudo coorte / Effectiveness of the triage system in a private emergency service: cohort study

Fundamentos: A superlotação dos serviços de emergência é um fenômeno mundial. Isto torna imprescindível que os sistemas de triagem utilizados sejam efetivos na identificação de atendimentos prioritários. Entretanto, pouco se conhece sobre a efetividade dos sistemas de triagem em serviços de emergência, principalmente na rede suplementar de saúde no Brasil. Objetivo: identificar a efetividade do sistema de triagem em serviço de emergência privado, baseado na Escala de Triagem Canadense. Métodos: Estudo coorte retrospectivo, com 254.730 registros de atendimentos, entre 2017 e 2018, de um serviço de emergência privado, referência em medicina de alta complexidade, em São Paulo (SP), Brasil. Estatística descritiva foi utilizada para caracterizar os atendimentos, de acordo com ano, sexo, idade, classificação de prioridade e desfecho clínico pós-atendimento. Associação entre os graus de prioridades da escala e os desfechos clínicos foi verificada pelo teste Qui-quadrado de Pearson. Para analisar efetividade do sistema de triagem foi delineado um modelo de regressão logística univariada, para prever o desfecho "internações/óbitos", em comparação com "altas". Devido ao tamanho amostral robusto, o nível de significância considerado foi de 0,1%. Resultados: Cerca de 60% dos atendimentos foram classificados como não urgentes e 30,8%, como urgentes. A probabilidade de morte e internação corresponderam ao aumentou do grau de prioridade, variando entre mais de 12 vezes para os atendimentos de "semi-urgência" a mais de 100 vezes para o grau "emergência". Pacientes atendidos no ano de 2018, do sexo masculino e com idade acima de 50 anos apresentaram maior probabilidade de serem internados ou morrerem. Conclusão: O sistema de triagem analisado foi considerado efetivo para prever desfechos clínicos compatíveis com a gradação de gravidade estabelecida. Isto é relevante na medida que expressa, pela primeira vez no Brasil, a efetividade em um sistema de triagem, baseado na Escala de Triagem Canadense. Além disso, a caracterização da busca expressiva por atendimentos de baixa gravidade entre usuários do serviço analisado é semelhante aos apresentados em diversos estudos nacionais e internacionais. Reflete-se sobre as explicações socioculturais e econômicas no contexto brasileiro, expondo perspectivas a serem atingidas por políticas públicas.Palavras-chave: Triagem, Medicina de emergências, Enfermagem em emergência, Estudos de coortes. (AU)

Background: the overcrowding of emergency services is a worldwide phenomenon. This makes it essential that the triage systems used are effective in identifying priority care. However, little is known about the effectiveness of triage systems in emergency services, especially in the supplementary health network in Brazil. Objective: identify the effectiveness of the triage system in a private emergency department, based on the Canadian Triage and Acuity Scale. Methods: a retrospective cohort study, with 254,730 records of care, between 2017 and 2018, from a private emergency service, reference in high complexity medicine, in São Paulo (SP), Brazil. Descriptive statistics were used to characterize the attendances, according to year, gender, age, priority rating, and post-acute clinical outcome. Association between the scale priority grades and clinical outcomes was verified by Pearson's chi-square test. To analyze the effectiveness of the screening system, a univariate logistic regression model was designed to predict the outcome "hospitalizations/hospitalizations" compared to "discharges". Due to the robust sample size, the significance level considered was 0.1%. Results: about 60% of the cases were classified as non-urgent and 30.8% as urgent. The probability of death and hospitalization corresponded to the increased degree of priority, ranging from more than 12 times for the "semi-urgent" attendances to more than 100 times for the "emergency" degree. Patients seen in 2018, male and over 50 years old, were more likely to be hospitalized or die. Conclusion: the screening system analyzed was considered effective in predicting clinical outcomes compatible with the established severity gradation. This is relevant as it expresses, for the first time in Brazil, the effectiveness of a triage system based on the Canadian Triage and Acuity Scale. Moreover, the characterization of the expressive search for low severity care among users of the analyzed service is similar to those presented in several national and international studies. Reflections on sociocultural and economic explanations in the Brazilian context are made, exposing perspectives to be achieved by public policies. (AU)

In a canine model, lung preservation at 10 degrees C is superior to that at 4 degrees C. A comparison of two preservation temperatures on lung function and on adenosine triphosphate level measured by phosphorus 31-nuclear magnetic resonance.

Techniques for organ preservation generally use hypothermia to retard metabolic requirements. However, excessive hypothermia may also produce injury. Using a canine left lung allotransplantation procedure, we compared two preservation temperatures (4 degrees and 10 degrees C) in terms of subsequent lung function measured by temporary occlusion of the right pulmonary artery after implantation of the preserved left donor lung. The lungs were flushed with low-potassium dextran electrolyte solution, inflated with 100% oxygen, and preserved for 18 hours. To investigate possible changes of energy stores at different temperatures, we performed phosphorus 31-nuclear magnetic resonance analyses of lung samples. Sequential determinations of adenosine triphosphate levels in lung tissue preserved at 4 degrees, 10 degrees, and 22 degrees C were studied. After transplantation, lungs preserved at 10 degrees C (n = 6) provided significantly better arterial oxygen tension than those preserved at 4 degrees C (n = 6), 451 +/- 46 mm Hg versus 243 +/- 86 mm Hg (p less than 0.05), and lower pulmonary vascular resistance, 581 +/- 68 dynes.sec.cm-5 versus 1006 +/- 157 dynes.sec.cm-5 (p less than 0.05). Adenosine triphosphate levels at 4 degrees and 10 degrees C were stable and did not differ from each other at the end of the 18-hour preservation period: 0.86 +/- 0.04 mumol/gm wet weight for control versus 0.86 +/- 0.07 mumol/gm wet weight for 4 degrees C and 0.93 +/- 0.06 mumol/gm wet weight for 10 degrees C after 18 hours of preservation. Preservation at 22 degrees C caused a 28% depression of adenosine triphosphate after 18 hours of preservation. These results lead us to conclude the following: (1) Optimal temperature for lung preservation is in the vicinity of 10 degrees C, and (2) lung dysfunction caused by excessive hypothermia is not due to a failure to maintain adenosine triphosphate levels. We suspect that adenosine triphosphate is generated by oxidative phosphorylation during lung preservation.

Improved bronchial healing in canine left lung reimplantation using omental pedicle wrap.

Bronchial complications are a major problem following lung transplantation. Ischemia of the donor bronchus is an important underlying cause of these complications. We have previously demonstrated the ability of an omental pedicle flap to revascularize the donor bronchus as early as 4 days following canine left lung reimplantation. In the present study, omental pedicle wraps markedly improved the healing of the bronchial anastomoses 23 days following canine left lung reimplantation. In dogs in which omentum was used (n = 6), the bronchial mucosal appearance was more normal and the degree of bronchostenosis was significantly less when compared with dogs without omental flaps (n = 10). These experiments suggest that the use of omental pedicle flaps may significantly reduce bronchial complications following lung transplantation.

Successful revascularization of totally ischemic bronchial autografts with omental pedicle flaps in dogs.

In 10 dogs, the left lung was removed and a closed stump of bronchus, comprising the distal main and lobar bronchi, was reanastomosed to the main bronchus. This totally ischemic cul-de-sac of bronchus was wrapped by an omental flap in five of the 10 dogs. All dogs without an omental wrap died of graft necrosis within 5 days. Injection studies into the bronchial arteries failed to demonstrate any revascularization of the bronchial grafts. In contrast, those dogs with omental wraps, when put to death at 23 days, displayed healthy viable bronchial grafts with full revascularization from the omental vessels. In another three dogs the revascularization via the omentum was demonstrated as early as 4 days and well established at 8 days. The ability of the omentum to rapidly revascularize the bronchus may be of value in potentially ischemic bronchial anastomoses such as in lung transplantation.

Evaluation of lung metabolism during successful twenty-four-hour canine lung preservation.

We used a canine left lung allotransplantation model to evaluate 24-hour lung preservation with two different electrolyte solutions, low-potassium dextran and low-potassium dextran with 1% glucose. To investigate changes in the energy status during preservation, we analyzed the lungs for adenosine triphosphate, phosphocreatine, and several metabolites of the glycolysis pathway and the citric acid cycle: glucose, glucose-6-phosphate, lactate, citrate, and malate. We also devised and evaluated a pulmonary cooling jacket to prevent rewarming of the lung during implantation. The lungs were divided into four groups. Groups I (n = 10) and II (n = 6) were flushed with low-potassium dextran and groups III (n = 6) and IV (n = 6) were flushed with low-potassium dextran solution with 1% glucose. The cooling jacket was used for groups II and IV only. After 24-hour preservation at 10 degrees C, the left lungs were implanted into the recipient animals. Function of the transplanted left lung was assessed during temporary (10 minutes) occlusion of the contralateral pulmonary artery while both lungs were ventilated with 100% oxygen. This assessment was performed at 1 hour and at 3, 8, and 22 days after transplantation. Immediately after transplantation the arterial oxygen tension was 279 +/- 70 mm Hg in group I, 376 +/- 56 mm Hg in group II, 523 +/- 41 mm Hg in group III, and 518 +/- 50 mm Hg in group IV. The arterial oxygen tension in groups III and IV were significantly greater than in group I (p < 0.05). Of the lungs preserved with low-potassium dextran solution with 1% glucose solution, 11 of 12 (92%) showed excellent lung function (arterial oxygen tension > 300 mm Hg) at 3 days; only 10 of 16 lungs preserved with low-potassium dextran achieved this level of function. Glucose, glucose-6-phosphate, lactate, citrate and malate levels decreased significantly during 24-hour preservation with low-potassium dextran solution; they were stable with low-potassium dextran solution with 1% glucose. Adenosine triphosphate and phosphocreatine were stable for 24 hours with both low-potassium dextran and low-potassium dextran solution with 1% glucose. The cooling jacket provided uniform cooling of the lung parenchyma during implantation, and significant increase in temperature was observed in its absence, with topical cooling by cold saline solution.(ABSTRACT TRUNCATED AT 400 WORDS)

A comparison between cyclosporin A and methylprednisolone plus azathioprine on bronchial healing following canine lung autotransplantation.

The effects of two low-dose immunosuppressive therapies upon the healing of the bronchial anastomosis and skin wounds following lung autotransplantation were evaluated. Autotransplantation was performed in three groups of dogs: Group 1 (nine dogs) received no immunosuppression, Group 2 (seven dogs) received postoperative immunosuppression with methylprednisolone (2 mg/kg) and azathioprine (1.5 mg/kg), and Group 3 (four dogs) received postoperative immunosuppression with cyclosporin A (20 mg/kg/day). Skin incisions 7 cm in length were made in the dorsal region of each dog. Dogs were put to death 23 days postoperatively, and the breaking strength of the bronchial anastomoses and skin wounds was evaluated with the Instron Universal Testing Machine, with a cross-head speed of 0.5 cm/min. Bronchial breaking strengths were similar in Groups 1 and 3 and significantly higher than in Group 2 (p less than 0.001). Skin breaking strengths were similar in Groups 1 and 3 and significantly higher than in Group 2 (p less than 0.001). Scanning electron microscopic (SEM) studies of both skin and bronchial wounds showed normal formation of collagen bundles in Groups 1 and 3 but a disorganized pattern in Group 2. Our results suggest that low-dose immunosuppression with methylprednisolone and azathioprine significantly affects wound healing and breaking strength of both bronchial anastomoses and healed skin incisions following canine lung autotransplantation. Immunosuppression with cyclosporin A had no adverse effect on either bronchial or skin healing.

Effects of methylprednisolone and azathioprine on bronchial healing following lung autotransplantation.

The effect of low-dose immunosuppressive therapy upon the healing of the bronchial anastomosis and skin wound following lung autotransplantation was evaluated. Autotransplantation was performed in two groups of dogs: Group 1 (15 dogs) received no immunosuppression and Group 2 (13 dogs) received postoperative immunosuppression with methylprednisolone (2 mg/kg) and azathioprine (1.5 mg/kg). Two to four skin incisions 7 cm in length were made in the dorsal region of each dog. Dogs were put to death at 4, 9, 16, and 23 days postoperatively and the bronchial anastomoses and skin wounds were evaluated by breaking strength measurements. Bronchus and skin breaking strength increased with time in both groups. Bronchus breaking strength was similar in the two groups at day 4 and day 9. However, by day 23 bronchus breaking strength was significantly higher in Group 1 (p less than 0.001). Skin breaking strength was significantly higher in Group 1 on days 9 and 16 (p less than 0.005) and on day 23 (p less than 0.001). Our results suggest that low-dose methylprednisolone and azathioprine significantly affect the breaking strength of both bronchial anastomoses and healing skin incisions following canine lung autotransplantation.

Virilizing Brenner tumor of the ovary: case report.

A case of ovarian Brenner tumor displaying androgenic activity and clinical masculinization is reported in a 65-year-old woman. Plasma androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone, dihydrotestosterone, cortisol, estradiol, FSH, LH, and prolactin were measured before and after suppression with dexamethasone and stimulation with hCG, and again after removal of the tumor. The plasma androgenic compounds were measured in both ovarian and peripheral veins. Basal levels of androstenedione and of total testosterone were significantly elevated, decreasing to normal ranges after operation and remaining after 3 months. There was a sharp increase of total testosterone, DHEAS, and dihydrotestosterone levels after administration of hCG. The levels of androstenedione, DHEAS, testosterone, and dihydrotestosterone were higher in the ovarian vein than in the peripheral vein. These findings indicate that the tumor was the main source of these androgenic hormones.

Lung preservation with low-potassium dextran flush in a primate bilateral transplant model.

We used a bilateral lung transplant model to confirm, in primates, the results of lung preservation studies previously obtained in a canine single-lung transplant model. The donor lungs were flushed with low-potassium dextran solution and maintained semiinflated with 100% oxygen at 10 degrees C for a planned ischemic time of 12 hours for the lung implanted first. Of eight experiments performed, results in the 6 operative survivors form the basis of this report. After bilateral lung transplantation, animals were maintained on a ventilator for 6 hours; arterial oxygen tension, pulmonary artery pressure, and pulmonary vascular resistance were determined in the recipients at 2, 4, and 6 hours after transplantation and compared with donor values, which served as controls. Arterial oxygen tension in the recipients did not differ from the controls (p = not significant), whereas the pulmonary artery pressure and pulmonary vascular resistance showed significant elevation (p < 0.05 versus control values). After the 6 hours of assessment, the animals were extubated and 3 survived for 48 to 72 hours with a mean arterial oxygen tension of 69 mm Hg on room air. These results demonstrate excellent lung function after a minimum of 12 hours of preservation in a primate model in which the animal is totally dependent on the function of transplanted lung tissue, and confirm the potential for prolonged clinical lung preservation.