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Background: The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD)., Methods: In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation., Results: There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category III, whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant [NS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11)., Conclusion: This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The clinical course of a patient with a left ventricular assist device is described. A total of 6 weeks after device insertion, the lactate dehydrogenase (LDH) level increased to 2801 U/l despite adding low-molecular-weight heparin to acenocoumarol and aspirin. Pump thrombosis was suspected but unconfirmed by computed tomography. Increased pump power requirement did not occur. Instituting unfractionated heparin caused a drop in the LDH level. After discontinuing heparin, the LDH levels rose to 5529 U/l whereupon pump replacement was performed. LDH levels, combined with clinical deterioration and right heart catheterisation, led to the diagnosis of pump thrombosis.

An unbalance between the platelet-adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off-pump lung transplantation. We analyzed plasma of 10 patients and distinguished lung transplantation-specific effects from those generally accompanying open-chest surgeries by comparing results with 11 patients undergoing off-pump coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for reference values. VWF antigen levels as well as the VWF ristocetin cofactor activity/VWF antigen ratio increased during lung transplantation and after CABG surgery. An increase in VWF propeptide levels was paralleled by a decrease in ADAMTS13 activity. This was more pronounced during lung transplantation. Similarly, the capacity of plasma to support platelet aggregation under shear flow conditions in vitro was more increased during lung transplantation. The proportion of high molecular weight VWF multimers was elevated in both groups without evidence for ultra-large VWF. VWF's collagen binding activity remained unchanged. In conclusion, a hyperactive primary hemostatic system develops during lung transplantation resulting both from a pronounced (functional) increase of the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet thrombosis within the allograft., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genome-wide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts., Methods: We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published., Results: We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended meta-analysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3., Discussion: We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our knowledge of genetic associations and BD, and provide further justification for pursuing collective initiatives in genetic studies given the low prevalence of this and other rare diseases.

South Africa has numerous thermal springs that represent topographically driven meteoric water migrating along major fracture zones. The temperature (40-70°C) and pH (8-9) of the thermal springs in the Limpopo Province are very similar to those of the low salinity fracture water encountered in the South African mines at depths ranging from 1.0 to 3.1 km. The major cation and anion composition of these thermal springs are very similar to that of the deep fracture water with the exception of the dissolved inorganic carbon and dissolved O2, both of which are typically higher in the springs than in the deep fracture water. The in situ biological relatedness of such thermal springs and the subsurface fracture fluids that feed them has not previously been evaluated. In this study, we evaluated the microbial diversity of six thermal spring and six subsurface sites in South Africa using high-throughput sequencing of 16S rRNA gene hypervariable regions. Proteobacteria were identified as the dominant phylum within both subsurface and thermal spring environments, but only one genera, Rheinheimera, was identified among all samples. Using Morisita similarity indices as a metric for pairwise comparisons between sites, we found that the communities of thermal springs are highly distinct from subsurface datasets. Although the Limpopo thermal springs do not appear to provide a new window for viewing subsurface bacterial communities, we report that the taxonomic compositions of the subsurface sites studied are more similar than previous results would indicate and provide evidence that the microbial communities sampled at depth are more correlated to subsurface conditions than geographical distance.

Rationale: Tuberculosis (TB) is a major cause of morbidity and mortality worldwide, thus there is an urgent need for novel TB vaccines., Objectives: We investigated a novel TB vaccine candidate, M72/AS01, in a phase IIa trial of bacille Calmette-Guérin-vaccinated, HIV-uninfected, and Mycobacterium tuberculosis (Mtb)-infected and -uninfected adults in South Africa., Methods: Two doses of M72/AS01 were administered to healthy adults, with and without latent Mtb infection. Participants were monitored for 7 months after the first dose; cytokine production profiles, cell cycling, and regulatory phenotypes of vaccine-induced T cells were measured by flow cytometry., Measurements and Main Results: The vaccine had a clinically acceptable safety profile, and induced robust, long-lived M72-specific T-cell and antibody responses. M72-specific CD4 T cells produced multiple combinations of Th1 cytokines. Analysis of T-cell Ki67 expression showed that most vaccination-induced T cells did not express Th1 cytokines or IL-17; these cytokine-negative Ki67(+) T cells included subsets of CD4 T cells with regulatory phenotypes. PD-1, a negative regulator of activated T cells, was transiently expressed on M72-specific CD4 T cells after vaccination. Specific T-cell subsets were present at significantly higher frequencies after vaccination of Mtb-infected versus -uninfected participants., Conclusions: M72/AS01 is clinically well tolerated in Mtb-infected and -uninfected adults, induces high frequencies of multifunctional T cells, and boosts distinct T-cell responses primed by natural Mtb infection. Moreover, these results provide important novel insights into how this immunity may be appropriately regulated after novel TB vaccination of Mtb-infected and -uninfected individuals., Clinical trial registered with www.clinicaltrials.gov (NCT 00600782).

Objectives: Mechanical circulatory support through left ventricular assist devices (LVADs) improves survival and quality of life for patients with end-stage heart failure who are ineligible for cardiac transplantation. Our aim was to calculate the cost-effectiveness of continuous-flow LVADs., Methods: A cost-utility analysis from a societal perspective was performed. A lifetime Markov model was set up in which continuous-flow LVAD was compared with optimal medical therapy (OMT). The treatment effect was modeled indirectly combining the results of the REMATCH trial comparing OMT with a pulsatile-flow LVAD and the HeartMate II Destination Therapy Trial comparing a pulsatile-flow LVAD with a continuous-flow LVAD. Cost data were based on real-world financial data of sixty-nine patients with a HeartMate II implantation from the University Medical Centre Utrecht (the Netherlands). One-way and probabilistic sensitivity analyses were performed., Results: Comparing the continuous-flow HeartMate II with OMT, 3.23 (95 percent confidence interval [CI], 2.18-4.49) life-years were gained (LYG) or 2.83 (95 percent CI, 1.91-3.90) quality-adjusted life-years (QALYs). The cost of an LVAD implant was approximately €126,000, of which the device itself represented the largest cost, being €70,000. Total incremental costs amounted to €299,100 (95 percent CI, 190,500-521,000). This resulted in an incremental cost-effectiveness ratio of €94,100 (95 percent CI, 59,100-160,100) per LYG or €107,600 (95 percent CI, 66,700-181,100) per QALY. Sensitivity analyses showed these results were robust., Conclusions: Although LVAD destination therapy improves survival and quality of life, it remains a relatively expensive intervention which renders the reimbursement of this therapy questionable.

Chronic kidney disease (CKD) is a common complication after lung transplantation (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking cessation for >6 months is required for LTx enlistment. However, the impact of smoking history on CKD development after LTx remains unclear. We investigated the effect of former smoking on CKD and mortality after LTx. CKD was based on glomerular filtration rate (GFR) ((125) I-iothalamate measurements). GFR was measured before and repeatedly after LTx. One hundred thirty-four patients never smoked and 192 patients previously smoked for a median of 17.5 pack years. At 5 years after LTx, overall cumulative incidences of CKD-III, CKD-IV and death were 68.5%, 16.3% and 34.6%, respectively. Compared to never smokers, former smokers had a higher risk for CKD-III (hazard ratio [HR] 95% confidence interval [95%CI]= 1.69 [1.27-2.24]) and IV (HR = 1.90 [1.11-3.27]), but not for mortality (HR = 0.99 [0.71-1.38]). Adjustment for potential confounders did not change results. Thus, despite cessation, smoking history remained a risk factor for CKD in LTx recipients. Considering the increasing acceptance for LTx of older recipients with lower baseline renal function and an extensive smoking history, our data suggest that the problem of post-LTx CKD may increase in the future., (©2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Since its discovery over two decades ago, the deep subsurface biosphere has been considered to be the realm of single-cell organisms, extending over three kilometres into the Earth's crust and comprising a significant fraction of the global biosphere. The constraints of temperature, energy, dioxygen and space seemed to preclude the possibility of more-complex, multicellular organisms from surviving at these depths. Here we report species of the phylum Nematoda that have been detected in or recovered from 0.9-3.6-kilometre-deep fracture water in the deep mines of South Africa but have not been detected in the mining water. These subsurface nematodes, including a new species, Halicephalobus mephisto, tolerate high temperature, reproduce asexually and preferentially feed upon subsurface bacteria. Carbon-14 data indicate that the fracture water in which the nematodes reside is 3,000-12,000-year-old palaeometeoric water. Our data suggest that nematodes should be found in other deep hypoxic settings where temperature permits, and that they may control the microbial population density by grazing on fracture surface biofilm patches. Our results expand the known metazoan biosphere and demonstrate that deep ecosystems are more complex than previously accepted. The discovery of multicellular life in the deep subsurface of the Earth also has important implications for the search for subsurface life on other planets in our Solar System.

Three experiments were conducted to assess brain damage resulting from percussive bolt shooting and cervical dislocation by crushing (neck crushing) in turkey hens (mean [se] bodyweight 11.4 [0.1] kg); percussive bolt shooting and blunt trauma in turkey toms (13.1 [0.2] kg); and percussive bolt shooting, blunt trauma and cervical dislocation by stretching (neck stretching) in broiler turkeys (3.9 [0.3] kg). Brain and skull damage were assessed using macroscopic and microscopic evaluations and CT. Macroscopic subcutaneous haemorrhage was significantly greater with the percussive bolt in all three experiments (hens P=0.01, toms P=0.02, broilers P=0.0003), and skull fractures were more severe for toms (P<0.0001) and broilers (P=0.03) killed with the percussive bolt versus blunt trauma. In a subsample of turkeys, microscopic brain damage was present in all turkeys killed by percussive bolt shooting (five hens, 10 toms and four broilers) and blunt trauma (nine toms and three broilers), but only in one of four turkeys killed by neck crushing and one of four turkeys killed by neck stretching. Percussive bolt shooting and blunt trauma most likely caused death by directly disrupting brain function, whereas neck stretching and neck crushing probably resulted in death from cerebral hypoxia and ischaemia.

Objectives. We aimed to compare the rate of apoptosis after cardiopulmonary bypass (CPB) and cardioplegic arrest during coronary artery bypass grafting (CABG) surgery between atrial and ventricular tissue.Methods. During CABG surgery with CPB and cardioplegic arrest, sequential biopsies were taken from the right atrial appendage and left ventricular anterior wall before CPB and after aortic cross clamp release. Change in number of apoptotic cells and biochemical markers of myocardial ischaemia and renal dysfunction were assessed.Results. CPB was associated with a transient small, but significant increase in CK (1091+/-374%), CK-MB (128+/-38%), troponin-T (102+/-13%) and NT-proBNP (1308+/-372%) levels (all: p<0.05). A higher number of apoptotic cells as assessed by caspase-3 staining was found in the ventricular biopsies taken after aortic cross clamp release compared with the biopsies taken before CPB (5.3+/-0.6 vs. 14.0+/-1.5 cells/microscopic field, p<0.01). The number of apoptotic cells in the atrial appendage was not altered during CPB. Correlation between the duration of aortic cross clamp time and the change in caspase-3 positive cells in the left ventricular wall was of borderline significance (r of 0.58, p=0.08). Similar results were obtained from TUNEL staining for apoptosis.Conclusion. CABG surgery with CPB and cardioplegic arrest is associated with an elevated rate of apoptosis in ventricular but not in atrial myocardial tissue. Ventricular tissue may be more sensitive to detect changes than atrial tissue, and may be more useful to investigate the protective effects of therapeutic intervention. (Neth Heart J 2010;18:236-42.).

Background: In most tuberculosis (TB) endemic countries, bacillus Calmette-Guérin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response., Methods: In a randomized clinical trial, BCG was administered intradermally either at birth (n=25) or at 10 weeks of age (n=21). Ten weeks after vaccination, and at 1 year of age, vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay., Results: Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells, particularly polyfunctional T cells co-expressing IFN-gamma, TNF-alpha and IL-2, and most strikingly at 1 year of age., Conclusions: Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response, when measured at 1 year of age.

Aims: To report long-term outcome data on the V technique using drug-eluting stents., Methods and Results: From April 2002 to December 2006, 31 consecutive patients were successfully treated with V stenting of a de novo bifurcation lesion. The technique involves the deployment of two stents in the two branches of a bifurcation, the proximal edges of the stents just touching one another. Patients exclusively received either sirolimus- (10), paclitaxel- (20) or biolimus-eluting (one) stents. On average, 1.5 +/- 0.8 stents with a total length of 26.6 +/- 17.2 mm and 1.1 +/- 0.4 stents with a total length of 18.3 +/- 7.6 mm were deployed in the distal main vessel and side branch respectively. Mean duration of follow-up was 853 +/- 553 days. Within 30 days, three patients died; two other patients had definite stent thrombosis involving the V stents, both requiring re-PCI. Beyond 30 days and within one year, there was one death and three cases of target vessel revascularisation, including one target lesion revascularisation. There were a further three deaths (one cardiac) beyond one year. Eleven patients (35.5%) had angiographic follow-up, exhibiting a binary restenosis rate of 9.1% at 203 +/- 33 days., Conclusions: In this real-world cohort, late clinical events stand in accord with studies on competitive techniques, but early outcome was less encouraging, probably due to the baseline risks.

Based on the changes in the field of heart transplantation and the treatment and prognosis of patients with heart failure, these updated guidelines were composed by a committee under the supervision of both the Netherlands Society of Cardiology and the Netherlands Association for Cardiothoracic surgery (NVVC and NVT).THE INDICATION FOR HEART TRANSPLANTATION IS DEFINED AS: 'End-stage heart disease not remediable by more conservative measures'.CONTRAINDICATIONS ARE: irreversible pulmonary hypertension/elevated pulmonary vascular resistance; active systemic infection; active malignancy or history of malignancy with probability of recurrence; inability to comply with complex medical regimen; severe peripheral or cerebrovascular disease and irreversible dysfunction of another organ, including diseases that may limit prognosis after heart transplantation.Considering the difficulties in defining end-stage heart failure, estimating prognosis in the individual patient and the continuing evolution of available therapies, the present criteria are broadly defined. The final acceptance is done by the transplant team which has extensive knowledge of the treatment of patients with advanced heart failure on the one hand and thorough experience with heart transplantation and mechanical circulatory support on the other hand. (Neth Heart J 2008;16:79-87.).

In the treatment of acute myocardial infarction, antithrombin and antiplatelet therapy are indicated according to the current guidelines. When a patient presents with symptoms and signs of acute myocardial infarction, an extensive list of diagnoses should be considered. Because of the nonspecific symptoms of aortic dissection, the disease may be easily misdiagnosed. A high clinical suspicion of aortic dissection is therefore required. Once aortic dissection has been diagnosed, surgical intervention provides the only definitive treatment for these patients, regardless of antithrombin and antiplatelet therapy.

Introduction: Early detection of prostate cancer is possible; overdetection of early disease that may never surface clinically during a lifetime is likely. On the other hand, early detection measures will detect life-threatening disease of which some maybe amenable to cure, while otherwise it would kill the patient. Proof of effectiveness of early detection is unavailable. Those who decide to be screened and those who decide not to be screened take risks that are difficult to balance against each other. How do we deal with this situation? What do we tell our patients?, Discussion: Ongoing randomized studies are likely to produce definitive answers on the question of whether screening will save men from prostate cancer deaths within a few years. The trials will also provide answers to the optimal way of screening and to the question of how to avoid overdiagnosis and treatment. In the meantime, however, men who are considering to undergo testing have a difficult decision to make. Our profession is obliged to provide assistance. The information provided unfortunately at this time cannot be the simple message: if you undergo testing your cancer will be detected early and be curable, so you will resolve the problem. It is necessary to stress the potential benefits and also the downside of testing. Elements of such information are provided in this article. Benefits may include the reassurance resulting from a normal test result, the early diagnosis of aggressive and still-curable cancer, and the avoidance of the consequences of advanced prostate cancer such as the occurrence of metastatic disease. The downside includes the possibility of missing prostate cancer and providing a false reassurance, the fact that screening may lead to unnecessary anxiety and medical tests when no cancer is present, and the fact that it may detect slow-growing cancer that may never cause any symptoms or shorten lifespan. All treatments have side effects to which men will be exposed, even those who do not have life-threatening cancer. In addition, there is no certainty that treatment will be successful., Conclusion: In the present situation, it is important to emphasize to patients that capabilities are being developed to identify those prostate cancers that may not cause any harm and to exclude them from immediate treatment. This recent development is a very important aspect for those who consider to be tested outside ongoing trials.

The treatment of Multiple Myeloma (MM), a malignant plasma cell disorder has changed considerably over the past decade. It has been convincingly shown that intensive treatment supported by autologous stem cell reinfusion is superior to conventional chemotherapy with alkylating agents or vincristine, doxorubicin and dexamethasone (VAD) alone in terms of a more rapid response and a longer disease-free survival. However, cure is not achieved in the majority of patients. Several trials have therefore focussed on repeated intensive treatments in order to improve the survival of these patients. Other approaches are aimed at identifying patients on the basis of prognostic factors, who may benefit from high-dose therapy. This review discusses the recent developments in intensive therapy for multiple myeloma.

Data relating to daily clinical practice were collected in an otologic database. Over a period of 3 years, information was gathered about 1,000 ear operations. This led to the following conclusions: the collection of data is difficult; the selection of data and the moment it should be fed into the systems are very important; there is a risk of using too many items and therefore reducing surgeon compliance. On the other hand, too few items result in irrelevant overviews. The collection of ear surgery data makes it easier to understand positive and negative outcomes.

A general protocol for the Pd-catalyzed-arylation of nitroalkanes is described. Substituted aryl bromides as well as aryl chlorides can be coupled efficiently with a variety of nitroalkanes under mild conditions to selectively yield the monoarylated products. This method tolerates a number of functional groups including ketones, esters, and olefins. Notably, the arylation of nitroalkanes can be effected chemoselectively over ketone and ester arylation.

Animals may act as bio-indicators for the pollution of soil, air and water. In order to monitor changes over time, a baseline status should be established for a particular species in a particular area. The concentration of minerals in soil is a poor indicator of mineral uptake by plants and thus their availability to animals. The chemical composition of body tissue, particularly the liver, is a better reflection of the dietary status of domestic and wild animals. Normal values for copper, manganese and cobalt in the liver have been established for cattle but not for African buffalo. As part of the bovine tuberculosis (BTB) monitoring programme in the Kruger National Park (KNP) in South Africa, 660 buffalo were culled. Livers (n = 311) were randomly sampled in buffered formalin for mineral analysis. The highest concentrations of copper were measured in the northern and central parts of the KNP, which is downwind of mining and refining activities. Manganese, cobalt and selenium levels in liver samples indicated neither excess nor deficiency; however, there were some significant area, age and gender differences. The results will be useful as a baseline reference when monitoring variations in the level and extent of mineral pollution on natural pastures close to mines and refineries.

Make your catalyst more enantioselective! The enantiomeric excess of a catalytic reaction system can sometimes be enhanced from below 10 to over 90 % by the use of suitable achiral additives. Since completely different mechanisms can influence the catalyst and reaction outcome, there is a range of additives that can be applied to improve the catalyst efficiency for a variety of organic reactions., (© 1999 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)

We investigated whether pulmonary surfactant in rat lung transplants recovered during the first week post-transplantation, along with symptoms of the reimplantation response, and whether this recovery was affected by early surfactant treatment. The severity of pulmonary injury was varied by transplanting left lungs with 6-h and 20-h ischemia (n = 12 and 19, respectively). Half of the transplants were treated by instillation of surfactant before reperfusion. Lungs from sham operated, and normal rats (n = 4 and 5, respectively) served as controls. The pulmonary injury severely impaired lung transplant function; 10 of the worst affected animals died. After 1 wk, symptoms of reimplantation response and properties of pulmonary surfactant were assessed. If untreated, the reimplantation response had almost resolved in the 6-h but not in the 20-h ischemia group; pulmonary surfactant, however, continued to be deficient in both ischemia groups (low amounts of surfactant phospholipids and surfactant protein A [SP-A]). Surfactant treatment improved the recovery from injury in the 20-h ischemia group resulting in normal lung function and amounts of surfactant phospholipids. Amounts of SP-A were not improved by surfactant treatment. In conclusion, early surfactant treatment enhances recovery from transplantation injury and is persistently beneficial for pulmonary surfactant in lung transplants.

An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was associated with an increase in alveolar surfactant components. Left lungs with 6-h (n = 8) or prolonged 20-h ischemia (n = 10) were transplanted syngeneically in rats. In both ischemia groups half of the lung transplants were treated with surfactant just before reperfusion. Lung function was measured during reperfusion for 1 h. Thereafter, the rats were killed and bronchoalveolar lavage was performed to measure alveolar surfactant components. We found that surfactant treatment improved the immediate function of lung transplants in parallel with a higher amount of total surfactant phospholipids, a higher percentage of the heavy subtype of surfactant, a normalized percentage of phosphatidylcholine, and a higher amount of endogenous surfactant protein A (SP-A). We conclude that surfactant treatment before reperfusion does improve the immediate lung transplant function in rats in association with an increase in alveolar surfactant components. More particularly, the amount of (endogenous) SP-A is thought to be crucial for the efficacy of surfactant treatment after lung transplantation.

Coarctation of the aorta and associated ventricular septal defect may be repaired simultaneously or by initial coarctation repair with or without banding of the pulmonary artery. The question is whether specific preoperative criteria can enable the surgeon to choose the optimal surgical management. Between 1980 and 1993, 80 infants younger than 3 months with coarctation and ventricular septal defect were treated surgically. In 64 infants (multistage group), simple coarctation repair was performed through a posterolateral approach, with concomitant banding of the pulmonary artery in 10 infants. Twenty ventricular septal defects were closed as a secondary procedure and four were closed as a tertiary procedure. Sixteen infants (single-stage group) underwent one-stage repair through an anterior midline approach. The total in-hospital mortality rate was 7.5%. Freedom from recoarctation after 5 years was 91.3% in the multistage group versus 60.0% in the single-stage group (p = 0.018). Freedom from secondary ventricular septal defect treatment in the multistage group after 5 years was 40.7%, versus 100% in the single-stage group (p = 0.016). Thirty-seven ventricular septal defects (47.8%) closed spontaneously. In particular, the preoperative left-to-right shunt and extension of the perimembranous VSD into the inlet or outlet were risk factors for the need for eventual surgical ventricular septal defect closure after initial coarctation repair. On the basis of these two risk factors, the probability of the need for eventual surgical treatment of ventricular septal defect after initial coarctation repair can be calculated. This policy offers a well-considered choice between single-stage and multistage repair, weighing the risk of secondary ventricular septal defect treatment versus the risk of recoarctation. Finally, the number of surgical procedures per infant will be as low as possible.

In this study we investigated the surfactant function in rat lung transplants at the peak of the reimplantation response in experimental groups with increasing warm ischemic times of the lung transplant. The left and right lungs in five groups of rats were assessed 24 hours after left lung transplantation: rats receiving transplants with lung graft ischemic times of 60 (n = 4), 90 (n = 5), and 120 (n = 5) minutes, donor rats with 120 minutes lung ischemia (n = 5) and normal (nonoperated) rats (n = 6). The reimplantation response was assessed by the ventilation score on chest roentgenograms, measurement of the static lung compliance, and the (serum) protein concentration in the bronchoalveolar lavage fluid. Surfactant in the bronchoalveolar lavage fluid was assessed by measuring the amount and the composition of surfactant phospholipids and the in vitro surfactant function in a pulsating bubble surfactometer. We found that longer ischemic times caused a more severe reimplantation response in the left lung grafts. Although the ventilation scores were equally low in the 60-, 90-, and 120-minute ischemia groups, the lung compliances decreased and the (serum) protein concentrations increased stepwise in correlation with longer ischemic times. The amount of surfactant phospholipids during the reimplantation response was not changed, but the percentage phosphatidyl choline decreased progressively in parallel with the severity of the reimplantation response. Finally, the in vitro function of surfactant from the lung transplants decreased in parallel with the prolongation of the ischemic time, whereas the function of surfactant from donor lungs with 120 minutes of ischemia and from native right lungs was not changed. We conclude that the surfactant function is impaired during the reimplantation response as a result of a high concentration of inhibiting serum proteins and a low percentage of phosphatidyl choline.

The optimal age for elective repair of aortic coarctation is controversial. The optimal age should be associated with a minimal risk of recoarctation, late hypertension, and other cardiovascular disorders. The purpose of this retrospective study is to determine the actuarial survival after aortic coarctation repair 25 years or more after operation and to calculate the optimal age for elective aortic coarctation repair. From 1948 to 1966, 120 consecutive patients underwent aortic coarctation repair. Eighty-seven were male (72.5%). The mean age at operation was 15.5 years (SD +/- 9.1 years). Resection and end-to-end anastomosis was performed in 103 patients (85.8%). Early mortality occurred in 6 patients as a result of surgical problems, whereas late mortality in 15 patients was predominantly caused by cardiac causes. The mean follow-up period was 32 years (range 25 to 44.2 years). Ninety-two patients 96.8%) were in New York Heart Association class I. The probability of survival 44 years after operation was 73%. Patients younger than 10 years at operation had the highest probability of survival at 97%. Multivariate analysis produced age at operation as the only incremental risk factor for the occurrence of recoarctation, of late hypertension, and of premature death. So that these sequelae can be avoided, elective aortic coarctation repair should be performed around 1.5 years of age. At that age, the probability of recoarctation will have decreased to less than 3%, and the probability of upper body normotension and long-term survival will be optimal.

We have modified the transcochlear approach to improve exposure of the anterior petrous apex, clivus, anterior cerebellopontine angle, and the prepontine region. These changes include resection of the external auditory canal, middle ear, glenoid fossa, and posterior zygomatic arch. This approach provides improved exposure of the petrous carotid artery, jugular bulb, and clivus. It offers the largest and most lateral access to the anterior cerebellopontine and prepontine region. The results of this approach in 11 patients are discussed.

The fiber gene of adenovirus type 41 was sequenced and compared to the fiber gene sequence of adenovirus type 40 (A. H. Kidd and M. J. Erasmus, 1989, Virology 172, 134-144), the other known member of subgroup F. The open reading frame, from map units 87 through 92 with transcription from the r-strand, comprised 1686 bases and was 45 bases longer than its counterpart on the Ad40 genome. The 45-base difference appears to have resulted from a block deletion on the Ad40 sequence. Apart from this one region, the Ad40 and Ad41 fiber genes showed remarkably high homology (95.6%), indicating a relatively recent evolutionary divergence. The deduced amino acid sequence of the Ad41 fiber polypeptide was analyzed according to the model of N. M. Green et al. (1983, EMBO J. 2, 1357-1365) for the structure of the adenovirus fiber. Ad41 had one more 15-residue repeat in the shaft region than Ad40, there being 22 repeat motifs. A detailed study of various Ad40 and Ad41 strains with proven genome differences indicated that the 15-amino acid difference in polypeptide length at the 14th repeat motif is a type-specific difference among the subgroup F adenoviruses. However, two uncommon Ad41 strains belonging to 2 of the 16 Ad41 genome types tested had a 15-amino acid block deletion which was different to that of the Ad40 polypeptide. The implication from this work is that the Ad40 fiber gene probably arose from its Ad41 counterpart, but the fiber gene sequences of both types of subgroup F adenovirus are so similar that genetic recombination between strains could occur with some frequency.

Chondroblastoma of the skull is a benign but locally aggressive tumor. In the past, simple curettage and radiation therapy have been advocated for treatment of this tumor. We present two patients with chondroblastoma of the temporal bone. The tumor extended through the dura in both patients and into the temporal lobe in one patient. Both patients were treated with wide local excision using a combined extended transmastoid and middle cranial fossa approach. On the basis of these two cases and a review of the literature, we recommend complete surgical excision as the primary treatment for chondroblastoma of the temporal bone.

A follow-up study, based on clinical, radiological and pathological information was performed of 20 patients who had suffered from an osteoid osteoma and of three patients who had been treated for an osteoblastoma in the period 1978-1988. 50% of the patients mentioned both pain at night and a good reaction to salicylates. In 87% of the cases a correct diagnosis was made with the aid of conventional radiography, tomography and bone scanning. Primary treatment consisted of intracapsular (mostly piecemeal) excision in all cases. A local recurrence was observed in one patient with osteoid osteoma and in two with osteoblastoma. At the time of this follow-up study none of the 23 patients had complaints. Histopathological examination did not reveal any difference between the two types of bone tumour.

The intricacies of the serological grouping of streptococci are discussed. The pathogenicity and accurate classification of streptococci isolated from arthritic porcine joints were in doubt. Pure cultures of these isolates were inoculated intravenously into healthy pigs to ascertain their pathogenicity and in an attempt to fulfil Koch's postulates. The pathogenesis of streptococcal arthritis in swine is discussed. On intravenous inoculation into experimental pigs the streptococcal isolates showed varying degrees of pathogenicity and arthritogenesis.

A newborn male presenting with congenital complete heart block was found to have low levels of free plasma carnitine. Among the many complications of carnitine deficiency is a structural disruption of myocardial tissue. A deficiency of carnitine may be causally related to the presence of cardiac dysrhythmias in this patient on the basis of mechanical disturbance to the cardiac conducting system.

Adult animals from a known negative and an infected herd were vaccinated with reduced-dose Brucella abortus strain 19 vaccine. Since some of these animals developed elevated post-vaccinal blood titres, it is suggested that, when adult vaccination is decided on, such herds should be bled and tested about 4 months after vaccination and thereafter at 2 month intervals. Reactions with complement fixation titres of 392 IU ml-1 or higher on the first test should be taken as positive. During the 2nd and 3rd tests, positive reactions should be taken as less than 98 IU ml-1 and 49 IU ml-1, respectively. After vaccination, an overkill of up to 5%, due to vaccination reactions could be expected. Positive cases might occur up to 9 months after vaccinating an infected herd. On farms selected for adult vaccination suitable calving facilities in isolation, largely facilitate eradication. Lochia samples for the early diagnosis of brucellosis should be collected. Adult vaccination with a reduced dose S 19 vaccine, should be practised on selected, problem herds only, where the owner is fully aware of the consequences of this procedure.

Homologous and heterologous haemagglutination-inhibition (HAI), complement-fixation (CF), immunodiffusion (ID) and mouse neutralization tests were performed with the Lunyo (LUN) and a Zimbabwean strain of Rift Valley fever (RVF) virus, the prototype and a South African strain of Arumowot (AMT) virus and prototype strains of Gordil (GOR), Saint-Floris (SAF) and Gabek Forest (GF) viruses, using immune mouse ascitic fluids prepared against these viruses. Reactions of identity occurred in all tests between LUN and the Zimbabwean strains of RVF and between the two strains of AMT virus. Otherwise, cross-reactions occurred between all the phleboviruses in HAI tests, while reactions in CF, ID and neutralization tests were monospecific for virus serotypes, except that weak cross-reaction occurred between GOR and SAF viruses in CF and ID tests. Four sheep infected subcutaneously with the Zimbabwean strain of RVF virus developed transient fever, viraemia, leucopaenia, relative thrombocytopaenia, haemoconcentration and raised serum enzyme levels, which indicated that the sheep had developed necrotic hepatitis. Disseminated focal necrotic hepatitis was confirmed in a sheep killed for examination on day 4 post-infection. The other three sheep recovered uneventfully after only mild depression and anorexia. Groups of three sheep infected with SAF, GOR, AMT and GF viruses had no demonstrable viraemia or other sign of infection or illness, except that the sheep infected with AMT developed mild fever lasting less than 24 h. Antibody responses were monitored at intervals over a period of 24 weeks in all sheep by homologous and heterologous HAI, CF and cell culture neutralization (CPENT) tests. Homologous antibody responses were marked in the RVF-infected sheep and their sera cross-reacted strongly in HAI tests with antigens of the other viruses. The sera of the RVF-infected sheep cross-reacted less markedly in CF and CPENT tests. Homologous antibody responses were poor in all the sheep infected with phleboviruses other than RVF, and the cross-reactivity of their sera for RVF antigen or virus was negligible. All sheep were challenged with RVF virus 48 weeks after their initial infection. The sheep which had originally been infected with RVF virus were immune and developed neither fever nor viraemia. All other sheep developed fever, viraemia and antibodies to RVF virus. It was concluded that the African phleboviruses, other than RVF, are unlikely to cause disease in livestock or to induce antibodies which could cause confusion in the diagnosis of RVF.

From February 1985 to January 1986, 432 stool samples, 310 from rural African children with diarrhea and 122 from controls, were analysed for the presence of enteric viruses known to be associated with diarrhea. Group A rotavirus ELISA indicated 12.9% positivity among patients and 2.5% positivity among controls. Only 23 of the 43 rotavirus ELISA-positive stools were also positive by electron microscopy. Nine children, three of whom were controls, were found to be shedding coronavirus-like particles, detected by electron microscopy. Stools from all but one of the nine children had been taken within 1 month of each other. Dot-blot hybridization tests for the presence of Ad40 or Ad41 DNA revealed 44 positive stools, 41 of which were from patients (13.2% positivity). Only three of the Ad40-or Ad41-positive stools by DNA hybridization were positive by electron microscopy, and only these three strains could be grown in semipermissive Chang conjunctival cells and their identity checked by restriction enzyme analysis. Further attempts to rescue the other strains using a helper virus failed, but nine of the stools proved positive by ELISA using a subgroup F-specific monoclonal antibody. On the basis of the DNA hybridization results alone, subgroup F adenoviruses were encountered as frequently as rotavirus in the study and were significantly associated with diarrhea, although the viability and intactness of virus particles by the time of laboratory analysis appeared to be very low.

The serological and biochemical characteristics of 100 strains of Streptococcus agalactiae isolated from quarter mild of dairy cows and of 107 strains cultured from various sites of human patients, were determined and compared. All the isolates were CAMP-phenomenon and Na-hippurate positive, aesulin negative, fell into Lancefield's Group B and could be placed into one of the 6 recognised serotypes. No human isolates fell into type R but for the rest all the other types were represented in the series of bovine and human cultures. In order of frequency, the human isolates were of type III, II, Ib, X and Ia and the bovine of type II, X, III, Ia, Ib and R. Of the human and bovine cultures respectively, 34 and 96% altered litmus milk, 30 and 100% were sensitive to bacitracin, 32 and 4% were pathogenic to mice, 82 and 93% reduced the ultimate pH of glucose broth to 4,2-4,8, 36 and 100% fermented lactose, 93 and 99% salicin and 94 and 79% trehalose. Concerning the combination of lactose/salicin fermentation, 35 and 95% of bovine and human isolates were , 0 and 5% were , 59 and 0% were -/=nd 7 and 0% were -/-. Data are summarised in 5 tables and discussed against the background of reports from other countries. It appears that a proportion of the human infections concern organisms likely to have been derived from bovine sources, either directly or indirectly. Definite classification of South African GBS into either human or animal strains does not seem possible. It is concluded that it would be more correct to refer to the source of an isolate instead of inferring that because the organism was primarily cultured from, say human resources, it is necessarily a human "strain'.

The fiber gene of human adenovirus type 40 has been characterized. The 6.1-kbp EcoRI fragment C of the Ad40 genome, from map units 74 through 92, was cloned and the right-most 2.8 kbp from 84 map units was sequenced. By analogy with Ad2, this region would be expected to contain the gene specifying the Ad40 fiber polypeptide. Sequencing revealed an open reading frame of 1641 bases on the r-strand, the first 53 bases of which had marked homology with the corresponding L5 (fiber) regions of Ad2 (77.2%), Ad5 (75.0%), and Ad3 (64.3%). In addition, base positions 1114 to 1146 of this open reading frame had 85% homology with base positions 1198 to 1230 of the Ad2 fiber gene. The predicted polypeptide sequence of 547 amino acids showed marked homology with the Ad2, Ad5, and Ad3 fiber polypeptides in two regions, in the first 55 amino acids from the N-terminus and from amino acids 372 through 382. Analysis of hydrophobic amino acid positions revealed a repeating pattern of approximately 15 residues between positions 42 and 374, with 21 repeats. The sequence of the Ad40 polypeptide thus fits the model of Green et al. [1983), EMBO J. 2, 1357-1365) for the structure of the adenovirus fiber, but is 35 amino acids shorter than the Ad2 fiber polypeptide, with one less 15-residue repeat in the shaft region. According to this model, the regions of highest homology between the Ad40 fiber polypeptide and those of Ad2, Ad5, and Ad3 correspond to the tail of the shaft and the base of the knob. The results of this analysis are in agreement with previously published EM data on the fiber length of subgroup F adenoviruses.

For comparison of the evaporative water loss through wound coverings, it is necessary to have an accurate and reliable method of measurement. The water vapour permeance (WVP), obtained with the Evaporimeter, meets these requirements, under both in vitro and in vivo circumstances.

Nine serological techniques were compared by monitoring the response to infection with Rift Valley fever (RVF) virus in three sheep. Antibodies were monitored daily for the first 14 days after infection, then weekly and later fortnightly up to week 24. The earliest antibody response was detected in one sheep on day 3 by a plaque reduction neutralization test, and by day 6 antibodies were demonstrable in all three sheep by haemagglutination-inhibition, reversed passive haemagglutination-inhibition, immunodiffusion, indirect immunofluorescence (IF), enzyme-linked immunosorbent assay and neutralization of cytopathic effect in cell cultures. Antibodies were demonstrable by complement fixation on day 8 at the earliest. IF and the two neutralization techniques produced the highest titres, but all tests could be used satisfactorily for the serological diagnosis of RVF. Inactivated antigen could be used for all except the neutralization tests. A radioimmunoassay technique using 125I-labelled staphylococcal protein A detected antibodies on day 8 at the earliest and produced lower mean titres than some of the other techniques. This was probably because sheep immunoglobulins bind protein A poorly.