Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro-inflammatory cytokines IL-4, IL-33 and TSLP.

BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities. OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research. METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.

IL-4 receptor α blockade prevents sensitization and alters acute and long-lasting effects of allergen-specific immunotherapy of murine allergic asthma.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only causal treatment for allergy. However, success rates vary depending on the type of allergy and disease background of the patient. Hence, strategies targeting an increased therapeutic efficacy are urgently needed. Here, the effects of blockade of IL-4 and IL-13 signaling on different phases of AIT were addressed. METHODS: The impact of the recombinantly produced IL-4 and IL-13 antagonist IL-4 mutein (IL-4M) on allergic sensitization and AIT outcome in experimental allergic asthma were analyzed in a murine model. The effects of IL-4M administration were assessed prior/during sensitization, immediately after AIT under allergen challenge, and two weeks post-treatment. RESULTS: Intervention with IL-4M prior/during sensitization led to strong induction of IgG1, IgG2a, IgG2b, and IgG3, decrease of specific and total IgE, as well as of IL-5 in serum. Similar effects on the serum immunoglobulin levels were observed immediately after IL4M-supplemented AIT during allergen challenge. Additionally, IL4M markedly suppressed type-2 cytokine secretion of splenocytes beyond the effect of AIT alone. These effects were equaled to those of AIT alone two weeks post-treatment. Intriguingly, here, IL-4M induced a sustained decrease of Th2-biased Tregs (ST2+ FOXP3+ GATA3intermediate ). CONCLUSIONS: IL-4 and IL-13 blockade during experimental AIT demonstrates beneficial effects on immunological key parameters such as immunoglobulin and cytokine secretion immediately after AIT. Although two weeks later these effects were dropped to those of AIT alone, the number of potentially disease-triggering Th2-biased Tregs was further significantly decreased by IL-4M treatment. Hence, IL-4/IL13-targeting therapies prime the immune memory in therapy success-favoring manner.

Identification of a plasma miRNA biomarker signature for allergic asthma: A translational approach.

BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach. METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.

Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells.

BACKGROUND: B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization. METHODS: B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days. RESULTS: Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation. CONCLUSIONS: Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.

Pollen-derived adenosine is a necessary cofactor for ragweed allergy.

BACKGROUND: Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation. METHODS: Aqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1-11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen-derived adenosine was removed from the extract enzymatically to analyze its role in ragweed-induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed-stimulated bronchial epithelial cells was analyzed. RESULTS: Instillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2-associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present. CONCLUSIONS: Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen-independent pathways.

Genome-wide, large-scale production of mutant mice by ENU mutagenesis.

In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).

Staged hybrid treatment of complex ascending aortic and distal aortic arch pseudoaneurysm after repair of aortic coarctation.

A 49-year-old operated for aortic coartaction patient presented with thoracic and ascending aortic aneurysm. He was asymptomatic. Angio-magnetic resonance nuclear scan and angiography revealed an ascending aortic aneurysm (5.2 cm), bicuspid aortic valve, 6-cm proximal descending aortic pseudoaneurysm at the site of the previous operation with involvement of the left subclavian artery. Restenosis at the original site of coarctation and aortic arch hypoplasia distally to the brachiocefalic trunk was also found. The operation performed was a "modified Bentall - De Bono". The pseudoaneurysm was not accessible through median sternotomy due to the massive lung adhesions following the previous surgery. The left common carotid artery was explanted from the aortic arch and connected with a graft to the ascending aortic conduit. A proximal neck suitable for landing zone of the endovascular stent-graft was then established. The postoperative course was uneventful. After two weeks, the patient was readmitted. The exclusion of the thoracic descending aortic pseudoaneurysm by endovascular implantation of the stent-graft prosthesis was performed. The left subclavian artery was excluded because left vertebral artery was closed. The patient did not develop hand claudicatio. The procedure was successful.

Suitability of miRNA assessment in postmortem interval estimation.

OBJECTIVE: The aim of this review was to explore recent pieces of evidence focused on the use of miRNAs for PMI estimation both in humans and animal experiments, with particular interest on the best miRNAs to use as reference/target markers in different tissues or biological fluids. MiRNAs are innovative biomarkers used in clinical and research field; they appear very attractive, being introduced in forensic research scenarios even for PMI estimation. MATERIALS AND METHODS: Data from PubMed and Scopus were analyzed from January 2013 to August 2020. Based on inclusion/exclusion criteria, high-quality articles have been selected to become the subject of this review. RESULTS: A total of 737 papers were found but, after titles/abstracts screening for inclusion criteria and a full-text careful selection, 33 papers were deeply studied. After the exclusion of 19 papers, 15 articles remained. Eight papers dealt with animals (mice/rats), two both with animals and humans (for method validation previously built), while 5 exclusively with humans. Myocardium (6/15) and brain (6/15) were the most studied tissues, respectively in mice/rats and humans. PMI considered was up to 7.5 days in mouse studies and less than 3 days in human models. CONCLUSIONS: Because of their significant stability in both early and long PMI, miRNAs are the cleverest reference markers to be used. Temperature and environmental conditions influence mostly mRNA, while miRNAs are less susceptible to them. The best miRNA to choose depends on its tissue specificity, i.e., miR-9 and miR-125 in brain or miR-1 and miR-133 in skeletal muscle/heart.

A Ge.F.I. - ISFG European collaborative study on DNA identification of Cannabis sativa samples using a 13-locus multiplex STR method.

Cannabis sativa is the most used controlled substance in Europe. With the advent of new and less restrictive European laws on cannabis sale for recreational use (including in Italy), an increase in indoor cannabis crops were observed. This increase was possible due to the availability of cannabis seeds through the internet market. Genetic identification of cannabis can link seizures and if in possession then might aid in an investigation. A 13-locus multiplex STR method was previously developed and validated by Houston et al. A collaborative exercise was organized by the Italian Forensic Geneticists - International Society of Forensic Genetics (Ge.F.I. - ISFG) Working Group with the aim to test the reproducibility, reliability and robustness of this multiplex cannabis STR kit. Twenty-one laboratories from three European countries participated in the collaborative exercise and were asked to perform STR typing of two cannabis samples. Cannabis DNA samples and the multiplex STR kit were provided by the University of Barcelona and Sam Houston State University. Different platforms for PCR amplification, capillary electrophoresis (CE) and genotyping software were selected at the discretion of the participating laboratories. Although the participating laboratories used different PCR equipment, CE platforms and genotyping software, concordant results were obtained from the majority of the samples. The overall genotyping success ratio was 96%. Only minor artifacts were observed. The mean peak height ratio was estimated to be 76.3% and 78.1% for sample 1 and sample 2, respectively. The lowest amount of -1 / + 1 stutter percentage produced, when the height of the parent allele was higher than 8000 RFU, resulted to be less than 10% of the parent allele height. Few common issues were observed such as a minor peak imbalance in some heterozygous loci, some artifact peaks and few instances of allelic drop-out. The results of this collaborative exercise demonstrated the robustness and applicability of the 13-locus system for cannabis DNA profiling for forensic purposes.

A case of acute fulminant multiple sclerosis treated with alemtuzumab.

We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture. This is the first reported case of Marburg type multiple sclerosis treated with alemtuzumab.

Clinical and angiographic effects of chronic calcium channel blocker therapy continued beyond first postoperative year in patients with radial artery grafts: results of a prospective randomized investigation.

BACKGROUND: This study was conceived to elucidate the clinical and angiographic effects of chronic calcium channel blocker therapy (CCCBT) continued after the first postoperative year in patients in whom the radial artery (RA) was used for myocardial revascularization. METHODS AND RESULTS: Patients who received RA grafts at our institution and who at 1 year had no scintigraphic evidence of ischemia in the RA territory or angiographic evidence of RA malfunction (n=120) were randomly assigned to continue (n=63) or suspend (n=57) the CCCBT with diltiazem (120 mg/d). After 5 years, all patients were reassessed clinically and by stress myocardial scintigraphy, and 87 of them (45 from the continued group that continued CCCBT and 42 from the group that suspended CCCBT) were restudied angiographically. No differences regarding either the clinical and scintigraphic results or the RA angiographic status were demonstrated between the 2 groups. CONCLUSIONS: After the first postoperative year, the continuation of CCCBT does not affect RA graft patency or clinical and scintigraphic results.

The unclampable ascending aorta in coronary artery bypass patients: A surgical challenge of increasing frequency.

BACKGROUND: The unclampable ascending aorta (UAA) is a condition increasingly encountered during CABG procedures. We report our experience with CABG patients with UAA and place particular emphasis on the preoperative diagnosis and surgical management. METHODS AND RESULTS: UAA was diagnosed in 211 of 4812 consecutive CABG patients (4.3%). On the basis of the chest radiograph, echocardiogram, and coronary angiograph, a preoperative diagnosis was achieved in only 58 patients (27.4%). An age of >70 years, diabetes, smoking, unstable angina, diffuse coronaropathy, and peripheral vasculopathy were all predictors of UAA. Patients were treated with hypothermic ventricular fibrillation (no-touch technique n=129) or beating heart revascularization (no-pump technique n=82) depending on the possibility of founding an arterial cannulation site. The overall in-hospital mortality rate was 2.8% (6 of 211) with no differences between the 2 surgical strategies. The no-touch technique was associated with a greater incidence of neurological complications (stroke and transient ischemic attack), renal insufficiency, and stay in the intensive care unit and hospital. However, at midterm follow-up, more patients of the no-pump group had ischemia recurrence. CONCLUSIONS: A preoperative diagnosis of UAA is achievable only in a minority of patients, which highlights the necessity revising the current diagnostic protocols. The use of the no-touch technique is associated with an high perioperative risk but a superior possibility of complete revascularization, whereas adoption of the no-pump strategy ensures a smoother postoperative course at the expense of an higher incidence of ischemia recurrence.

Gamma knife radiosurgery in brain metastases from testicular tumors.

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8-2.0 Gy. The indications for radiosurgery were tumor volume <20 cm3, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with 1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.

The level of prosaposin is decreased in the skin of patients with psoriasis vulgaris.

Ceramides are the most abundant lipids constituting the intercellular matrix of the skin stratum corneum and their critical role in skin homeostasis has been extensively documented. Their concentration in the skin highly depends on the rate of availability of the enzymes involved in ceramide generation. The aim of this study was to investigate whether the concentration of prosaposin was altered in the skin of patients with psoriasis vulgaris. Prosaposin, the precursor of saposins (sphingolipid activator proteins), was measured in lesional and nonlesional skin of psoriatic patients and in normal skin from surgical patients, both at the mRNA and at the protein level. Densitometric analysis of reverse transcriptase-polymerase chain reaction bands separated by gel-electrophoresis showed a progressive decrease of prosaposin mRNA expression in nonlesional and lesional psoriatic skin, being substantially decreased in lesional psoriatic skin compared with normal control skin. Immunohistochemical analysis showed a significant decrease of prosaposin level in the stratum corneum of psoriatic lesional skin (both in active-type and in chronic-type plaque) compared with nonlesional and with normal skin (p < 0.01), and in psoriatic nonlesional skin compared with normal control (p < 0.05). Immunolocalization of sphingomyelinase in lesional and nonlesional psoriatic skin showed a decrease in the level of this enzyme in the stratum corneum of psoriatic lesional, compared with nonlesional skin. These results support the concept that disturbance of epidermal barrier function caused by derangement in ceramide generation can be crucial for the development of psoriatic skin diseases.

Implicit redundant-targets effect in visual extinction.

Patients with left visual extinction as a result of unilateral right hemisphere damage were tested on a redundant-targets effect paradigm (RTE). LED-generated brief flashes were lateralized either to the left or to the right visual hemifield or presented bilaterally. Subjects were asked to press a key as fast as possible following either unilateral or bilateral stimuli and immediately afterwards to report on the number of stimuli presented. As previously found in normal subjects, bilateral stimuli were responded to faster than unilateral ones, and this was evidence of a RTE. The main thrust of this study was that extinction patients showed a RTE not only for correctly perceived bilateral stimuli but also in trials in which they extinguished the stimulus on the field contralateral to the lesion. This result is compatible with a preserved processing of the extinguished input at least up to the stage at which it may interact with the input from the normal side to yield a speeded motor response. Interestingly, the implicit redundancy gain of extinction patients was found to fit a coactivation (i.e. neural) rather than a probabilistic model.

Enhancement of extended lung preservation with a vasoactive intestinal peptide-enriched University of Wisconsin solution.

Vasoactive intestinal peptide (VIP) is a known pulmonary and bronchial vasodilator as well as an oxygen free radical scavenger. Since its effect as an additive to University of Wisconsin (UW) solution for lung preservation has been shown previously, the aim of this study was to determine the ability of VIP to improve lung preservation followed by reperfusion. Four groups of excised Sprague-Dawley rat lungs (n = 24) were studied using an isolated blood perfused working lung model. The first 3 groups of lungs were flushed and stored in UW solution at 4 degrees C for: (1) 4 hr, (2) 18 hr, and (3) 24 hr. Group 4 lungs were flushed with UW solution + VIP (1 microgram/ml) and stored in UW solution + VIP (0.5 microgram/ml) for 24 hr. After preservation, the lungs were reperfused to evaluate their functions for 2 hr or until lung failure occurred (arterial oxygen saturation less than 90% and/or appearance of bronchial fluid in the bronchial cannula). In the lungs stored in UW solution for 24 hr, failure occurred after 10 min of reperfusion and all functions were significantly altered. The addition of VIP to UW solution maintained the functional capacity of the lungs, recorded by lung resistance, lung compliance, elastic work, flow resistive work, shunt fraction, and blood oxygen tension. No statistical difference in these parameters other than shunt fraction was found when the VIP group was compared with the group preserved for 4 hr in UW solution. We conclude that lung preservation can be extended to 24 hr with the maintenance of lung functional capacity if VIP is added to UW solution.

Vasoactive intestinal peptide enhances lung preservation.

The outcome of lung transplantation is often dependent on the quality of the donor lungs. To explore a way to improve lung preservation, vasoactive intestinal peptide (VIP) was added to pneumoplegic solutions. The 4 solutions tested were Krebs solution, Krebs solution with VIP, University of Wisconsin solution, and the University of Wisconsin solution with VIP. The lungs of 8 male Sprague-Dawley rats were flushed and stored in these solutions for 24 hr. At regular intervals, tissue was sampled and examined by light, scanning, and transmission electron microscopy. Casts of the vasculature were made after 4 hr and viewed by a scanning electron microscope. Lungs appeared well preserved by light microscopy at all intervals. Although inflammatory cells around arteries, arterial constriction, bronchiolar epithelial detachment, peribronchiolar edema, and alveolar size inhomogeneity were greater with time, there was no significant difference among the 4 groups by light microscopy. Scanning microscopy of tissue at 24 hr confirmed the information found on light microscopy but did not allow separation of the groups. The vascular casts showed that edema around large vessels was less in the lungs treated with VIP (P < 0.01). Transmission electron microscopy showed that lungs stored in the solutions with VIP had significantly more normal-shaped mitochondria, less mitochondrial edema, less distortion of mitochondrial cristae, thinner basal lamina, and less aggregation of nuclear chromatin at most intervals sampled after 4 hr. We conclude that VIP added to certain pneumoplegic solutions improves the ultrastructure of rat lung stored in the cold for up to 24 hr. VIP may be an important additive to pneumoplegic solutions to improve preservation of lung before transplantation.

Impact of initial flush potassium concentration on the adequacy of lung preservation.

The effects of initial lung flushing with intracellular and extracellular fluid type solutions were studied in lungs stored with the University of Wisconsin solution. Excised Sprague-Dawley rat lungs (n = 39) were flushed first with one of the following solutions: (1) the University of Wisconsin solution (K+ = 140 mmol/L), (2) modified (low potassium) University of Wisconsin solution (K+ = 20 mmol/L), (3) phosphate buffered saline solution (K+ = 3.9 mmol/L), (4) modified low-potassium phosphate-buffered saline solution (K+ = 20 mmol/L), (5) modified high-potassium phosphate-buffered saline solution (K+ = 40 mmol/L), and (6) Euro-Collins solution (K+ = 115 mmol/L) followed by secondary flush with storage solution and cold (4 degrees C) storage in University of Wisconsin solution for 24 hours. The lungs were then reperfused in the isolated, pulsatile, blood-perfused working lung system for 2 hours or until lung failure. Blood gas analysis and shunt fraction, aerodynamic parameters (airway resistance, lung compliance, elastic work, and flow resistive work), and total pulmonary vascular resistance were measured throughout the perfusion period. The mean oxygen tensions (in millimeters of mercury) at 30 minutes after the onset of reperfusion for University of Wisconsin solution, modified University of Wisconsin solution, phosphate-buffered saline solution, modified phosphate-buffered saline solutions (20 and 40 mmol/L), and Euro-Collins solution were 56.1 +/- 4.2, 72.7 +/- 9.1, 87.7 +/- 6.9 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), 86.0 +/- 9.6 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), 87.9 +/- 7.7 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), and 53.5 +/- 6.0, respectively. All aerodynamic parameters in the lungs flushed with extracellular fluid type solutions were superior to those flushed with intracellular fluid type solutions. We conclude that the efficacy of initial flushing was essential for successful lung preservation and that extracellular fluid type solutions were superior to intracellular fluid type solutions, at least for flushing the lung before storage with University of Wisconsin solution. Potassium concentration in flushing solution should be 20 mmol/L or less to obtain appropriate flushing and subsequent adequate distribution of the storage solution.

Systematic clinical and angiographic follow-up of patients undergoing minimally invasive coronary artery bypass.

OBJECTIVE: We herein analyze the results of the systematic clinical and angiographic control performed in a series of 77 consecutive patients undergoing minimally invasive coronary artery bypass. METHODS AND RESULTS: From January 1995 to June 1997, 77 patients underwent minimally invasive coronary artery bypass at our institution. There was one inhospital death, one noncardiac late death, and five patients had to be reoperated for graft malfunction. A total of 76 patients underwent postoperative angiographic follow-up. In 66 cases (86.8%) the thoracic artery graft, the target vessel, and the anastomosis were patent and functioning normally. In one case the graft was occluded. In the remaining nine cases the thoracic artery graft was patent but with major anomalies of either the anastomosis, the target vessel, or the course of the thoracic artery. Patients operated using especially designed instruments had angiographic results clearly superior to those of patients operated using conventional instrumentation (perfect patency rate 100% vs 81.8%). At a mean follow-up of 18 months, 98.5% of the surviving patients are asymptomatic with negative myocardial scintigraphy. CONCLUSIONS: The perfect patency rate of minimally invasive revascularization performed without the use of dedicated instruments is unacceptably low. The use of specific devices is likely to result in a substantial improvement in the angiographic results.

Coronary angiodysplasia of epicardial and intramural vessels.

A case of coronary angiodysplasia combining large aneurysms of epicardial arteries with diffuse malformation of intramural vessels is reported. Clinical presentation may mimic a vascularized cardiac tumor. Although leaking of the aneurysms in the pericardial space may occur, this entity seems to have a benign prognosis not requiring surgical repair.