[Epidemiology, Clinical Presentation, Diagnosis and Treatment of Infections Caused by Mycobacterium chimaera]. / Epidemiologie, Klinik, Diagnostik und Therapie von Infektionen durch Mycobacterium chimaera.

The recognition, correct diagnosis and adequate clinical management of infections caused by atypical mycobacteria are challenging tasks in clinical practice. Invasive infections caused by Mycobacterium chimaera, a member of the Mycobacterium avium-intracellulare complex, have been increasingly reported over the past few years. Most infections occurred in patients who had undergone open-chest cardiothoracic surgery. Epidemiological and molecular studies showed that transmission of M. chimaera occurred through intraoperative aerosols derived from contaminated heater-cooler units, i. e. devices that are used to enable the extracardiac circuit in cardiothoracic surgery. Thus far, approximately 120 patient cases have been reported worldwide. The latency between exposure and onset of clinical symptoms may comprise several years. Clinical manifestations of M. chimaera infections include not only endocarditis and implant-associated infections, but also non-cardiac entities such as sarcoidosis-like symptoms, vertebral osteomyelitis and chorioretinitis. The pathogen can be detected in blood culture vials and in surgically obtained specimens from affected tissues, if specific microbiological tests for detection of mycobacteria are employed. There are no simple-to-use screening tests and a high clinical index of suspicion is thus mandatory in patients with previous exposure and compatible signs and symptoms. The successful treatment of M. chimaera infections requires the removal of infected devices and prolonged combination therapy with antimycobacterial drugs. This review summarises the clinical relevance, epidemiology, symptomatology, diagnosis and treatment of infections caused by M. chimaera, with a specific focus on pneumological aspects.

Vasopressin induces rectosigmoidal mucosal ischemia during cardiopulmonary bypass.

BACKGROUND: Lower gastrointestinal complications are rare after cardiac surgery with cardiopulmonary bypass (CPB). However, if they occur, they are associated with a high mortality. Endothelin (ET) expression and microcirculatory dysfunction have been shown to be involved in a variety of diseases of the lower gastrointestinal tract. The aim of this study was to analyze whether CPB with or without additional vasopressin administration affects the rectosigmoidal mucosal microcirculation and whether this involves the ET system. METHODS: Pigs were randomized in three groups (n = 6 each): I Sham, II CPB: 1 hour CPB, III CPB + vasopressin: 1 hour CPB and vasopressin (0.006 U/min kg) administration maintaining baseline arterial pressure. All animals were reperfused for 90 minutes. During the experiment hemodynamics and rectosigmoidal mucosal microcirculation were measured continuously. The rectosigmoidal mucosal expression of endothelin-1 (ET-1) and its receptor subtypes A (ETA ) and B (ETB ) were determined using PCR and Western blot analysis. RESULTS: CPB did not change rectosigmoidal microvascular blood flow compared to baseline (68.1 ± 4.0 vs. 75.5 ± 6.6 AU; p = 0.4), but increased ET-1 (gene, 7.8 ± 1.5 vs. 2.3 ± 0.6 RQ; p = 0.002 and protein, 12.0 ± 0.5 vs. 6.9 ± 0.3 OD mm(2) ; p < 0.001), ETA (gene, 2.3 ± 0.6 vs. 0.6 ± 0.1 RQ; p < 0.001 and protein, 11.0 ± 0.3 vs. 6.2 ± 1.1 OD mm(2) ; p = 0.006) and ETB (gene, 6.7 ± 1.2 vs. 1.9 ± 0.3 RQ; p < 0.001 and protein, 25.6 ± 1.4 vs. 14.9 ± 1.5 OD mm(2) ; p = 0.002) expression compared to Sham. Vasopressin during CPB reduced the rectosigmoidal blood flow compared to baseline (26.5 ± 4.9 vs. 75.5 ± 6.6 AU, p < 0.001), and blunted the CPB-induced increase of ET-1 (gene, 1.2 ± 0.4 RQ, p = 0.1 and protein, 8.1 ± 1.6 OD mm(2) , p = 0.5 vs. Sham), ETA (gene, 0.6 ± 0.1 RQ, p = 1.0 and protein, 7.0 ± 0.6 OD mm(2) , p = 0.6 vs. Sham) and ETB (gene, 1.3 ± 0.3 RQ, p = 0.1 and protein, 19.4 ± 2.1 OD mm(2) , p = 0.1 vs. Sham). CONCLUSION: CPB does not significantly affect rectosigmoidal mucosal microcirculation; however, it upregulates ET-1, ETA , and ETB . Vasopressin blunts the CPB-induced elevation of ET-1, ETA , and ETB and induces rectosigmoidal mucosal ischemia during CPB.

Laser assisted pulmonary metastasectomy promises a low local recurrence rate.

Pulmonary metastasectomy (PM) is consensually performed in a parenchyma-sparing manner to preserve functionally healthy lung tissue. However, this may increase the risk of local recurrence at the surgical margin. Laser assisted pulmonary metastasectomy (LPM) is a relatively recent innovation that is especially useful to resect multiple metastatic pulmonary nodules. In this study we investigated the rate of local recurrence after LPM and evaluated the influence of various clinical and pathological factors on local recurrence. Retrospectively, a total of 280 metastatic nodules with different histopathological entities were studied LPM from 2010 till 2018. All nodules were resected via diode-pumped neodymium: yttrium-aluminum-garnet (Nd:YAG) 1,318 nm laser maintaining a safety margin of 5 mm. Patients included were observed on average for 44 ± 17 months postoperatively. Local recurrence at the surgical margin following LPM was found in 9 nodules out of 280 nodules (3.21%). Local recurrence at the surgical margin occurred after 20 ± 8.5 months post operation. Incomplete resection (p = < 0.01) and size of the nodule (p = < 0.01) were associated with significantly increased risk of local recurrence at the surgical margin. Histology of the primary disease showed no impact on local recurrence. Three and five-year survival rates were 84% and 49% respectively. Following LPM, the rate of local recurrence is low. This is influenced by the size of the metastatic nodules and completeness of the resection. Obtaining a safety margin of 5 mm seems to be sufficient, larger nodules require larger safety margins.

A 13-year-old girl with arterial hypertension - mid-aortic syndrome.

Mid-aortic stenosis (MAS) is a rare clinical entity that is characterised by profound narrowing of the abdominal aorta. MAS usually presents with severe hypertension. Treatment modalities include antihypertensive medication, angioplasty, and surgery. If adequate treatment is initiated long-term prognosis is favourable. Here, we report on 13-year-old girl with MAS who presented to our hospital with arterial hypertension. Initial diagnostic work-up and treatment in patients with MAS are presented.

[Carotid artery stenosis: current state of therapy]. / Karotisstenose: Aktueller Stand der Therapie.

Ipsilateral occlusive or embolizing carotid artery stenoses are found in 20-30% of all cases of ischemic stroke. Several randomized studies revealed endarterectomy to be the gold standard in the therapy of severe symptomatic (NASCET, ESCT) and to some extent of asymptomatic carotid stenoses (ACAS, ACST). Stent angioplasty has been established as an alternative therapeutic option although non-inferiority of this procedure has not yet been proven. We provide an overview of both procedures as well of the state of current trials.

Bilateral papillary muscle repositioning: successful repair of functional mitral regurgitation in dilative cardiomyopathy.

OBJECTIVES: Functional mitral regurgitation (FMR) in patients with non-ischaemic dilative cardiomyopathy (DCM) is associated with heart failure and poor outcome. Aggressively undersized annuloplasty as an annular solution for a ventricular problem ameliorates heart failure but may be associated with recurrent FMR and does not improve survival. We sought to analyse if moderately undersized annuloplasty with repositioning of both papillary muscles can lead to improved valve stability and outcome in patients with DCM and FMR. METHODS: In 66 patients with DCM-associated FMR (age 66 ± 12 years, ejection fraction 29 ± 6% and mean pulmonary artery pressure 35 ± 11 mmHg) and severe leaflet tethering (tenting height ≥10 mm) bilateral papillary muscle repositioning was added to moderately undersized ring annuloplasty (median size 30 mm). Concomitant surgery included tricuspid valve repair in 86% of patients and atrial ablation in 44%. RESULTS: The early mortality rate was 9%. Overall 5-year freedom from all-cause death, left ventricular assist device implantation or heart transplant was 58% (95% confidence interval 45-71%). Six patients underwent reoperation (redo repair n = 4). Reverse remodelling was observed during follow-up in 66% of patients with decreasing left ventricular end-diastolic diameters (66 ± 5 to 61 ± 12 mm; P < 0.001) and left ventricular end-systolic diameters (56 ± 9 to 51 ± 14 mm; P = 0.001). Subgroup analyses (partial versus complete ring, preoperative left ventricular end-diastolic diameters <65 mm vs left ventricular end-diastolic diameter ≥65 mm) documented similar survival rates. A competing risks regression analysis identified cerebral vascular disease (P = 0.01), use of a partial ring (P = 0.03) and absence of tricuspid valve repair (P = 0.03) as independent predictors of death. CONCLUSIONS: The combination of bilateral papillary muscle repositioning and moderately undersized ring annuloplasty leads to stable mid-term repair results and reverse remodelling in patients with DCM and FMR and severe leaflet tethering.

Impaired detection of Mycobacterium tuberculosis immunity in patients using high levels of immunosuppressive drugs.

We have previously shown, in renal transplant recipients on maintenance immunosuppression, that a whole-blood assay was superior in detecting immunity towards purified protein derivative (PPD) compared with skin testing. As blood tests may have limitations during high-dose immunosuppression therapy, the present study was aimed at characterising the effect of high immunosuppressive drug levels on PPD-specific T-cell immunity. PPD-reactive CD4 T-cells from 13 renal transplant recipients were longitudinally quantified by the induction of cytokines using flow cytometry. To further address the effect of high and low maintenance immunosuppression, drug effects were studied in vitro and in 49 age-matched lung transplant recipients and 49 renal transplant recipients. Maintenance immunosuppression after renal transplantation did not affect PPD-specific T-cell detection (median T-cell frequencies 0.55% before and 0.46% >12 months after transplantation), whereas specific T-cell frequencies were significantly lower 3 months after transplantation (0.15%; p = 0.0002). Likewise, high-level maintenance immunosuppression after lung transplantation was associated with a significantly lower prevalence in PPD-specific T-cell reactivity compared with renal transplant recipients (16.7% versus 52.1%; p = 0.0005). In line with the observations made in vivo, calcineurin inhibitors analysed in vitro led to a dose-dependent decrease in antigen-specific T-cell reactivity. The flow cytometric assay is not adversely affected by low drug doses. In contrast, decreased levels of PPD-specific T-cells early after transplantation and low prevalence of PPD-reactivity in lung transplant recipients suggest a reduced sensitivity of in vitro testing during high-level immunosuppression.

Risk factors for chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by nonresolving pulmonary thromboemboli that can be treated by surgical pulmonary endarterectomy (PEA). The authors of the present study sought to confirm known and to identify novel CTEPH risk factors in a controlled retrospective cohort study of prevalent CTEPH cases collected in three European centres offering PEA. Data from CTEPH patients were compared with nonthromboembolic pre-capillary pulmonary arterial hypertension cohorts at the participating institutions. The study population comprised 687 patients assessed at the time of diagnosis between 1996 and 2007. Ventriculo-atrial shunts and infected pacemakers (odds ratio (OR) 76.40, 95% confidence interval (CI) 7.67-10,351), splenectomy (OR 17.87, 95% CI 1.56-2,438), previous venous thromboembolism (VTE; OR 4.52, 95% CI 2.35-9.12), recurrent VTE (OR 14.49, 95% CI 5.40-43.08), blood groups other than 0 (2.09, 95% CI 1.12-3.94), and lupus anticoagulant/antiphospholipid antibodies (OR 4.20, 95% CI 1.56-12.21) were more often associated with CTEPH. Thyroid replacement therapy (OR 6.10, 95% CI 2.73-15.05) and a history of malignancy (OR 3.76, 95% CI 1.47-10.43) emerged as novel CTEPH risk factors. In conclusion, the European database study confirmed previous knowledge of chronic thromboembolic pulmonary hypertension risk factors, and identified thyroid replacement therapy and a history of malignancy as new medical conditions associated with chronic thromboembolic pulmonary hypertension.

The PPAR-gamma agonist rosiglitazone facilitates Akt rephosphorylation and inhibits apoptosis in cardiomyocytes during hypoxia/reoxygenation.

BACKGROUND AND AIM: Results on the cardiovascular effects of PPAR-gamma agonists are conflicting. On one hand, it was suggested that the PPAR-gamma agonist rosiglitazone may increase the risk of cardiovascular events. On the other hand, PPAR-gamma agonists reduce myocardial infarct size and improve myocardial function during ischemia/reperfusion in animal studies in vivo. However, the mechanism of this effect is unclear, and it is open if PPAR-gamma agonists have a direct effect on cardiac myocyte survival in ischemia/reperfusion. The aim of this study was to determine the effect of the PPAR-gamma agonist rosiglitazone on hypoxia/reoxygenation-induced apoptosis of isolated cardiomyocytes. METHODS: Isolated rat cardiac myocytes were pretreated with rosiglitazone or vehicle for 30 min before they were subjected to hypoxia for 4 h followed by different times of reoxygenation (5 min to 12 h). Apoptosis was determined by in situ hybridization for DNA fragmentation (TUNEL) as well as detection of cytoplasmic accumulation of histone-associated DNA fragments by enzyme-linked immunosorbent assay (ELISA). Activation of apoptosis regulating intracellular signalling pathways was studied by immunoblotting using phosphospecific antibodies. RESULTS: Rosiglitazone significantly reduced apoptosis of isolated cardiomyocytes subjected to hypoxia/reoxygenation, independently determined with two methods. After 4 h of hypoxia and 12 h of reoxygenation, 34 +/- 3.6% of the vehicle treated cardiac myocytes stained positive for DNA fragmentation in the TUNEL staining. Rosiglitazone treatment reduced this effect by 23% (p < 0.01). Even more pronounced, cytoplasmic accumulation of histone-associated DNA fragments detected by ELISA was reduced by 35% (p < 0.05) in the presence of rosiglitazone. This inhibition of hypoxia/reoxygenation-induced apoptosis was associated with an increased reoxygenation-induced rephosphorylation of the protein kinase Akt, a crucial mediator of cardiomyocyte survival in ischemia/reperfusion of the heart. This effect was reversed by GW-9662, an irreversible PPAR-gamma antagonist. However, rosiglitazone did not alter phosphorylation of the MAP kinases ERK1/2 and c-Jun N-terminal kinase (JNK). CONCLUSION: It can be concluded that cardiac myocytes are direct targets of PPAR-gamma agonists promoting its survival in ischemia/reperfusion, at least in part by facilitating Akt rephosphorylation. This effect may be of clinical relevance inhibiting the reperfusion-induced injury in patients suffering from myocardial infarction or undergoing cardiac surgery.

[Chronic thromboembolic pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option - as PEA - is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.

Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.

BACKGROUND: The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown. METHODS AND RESULTS: In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment. CONCLUSION: An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.

Complete arterial revascularization in multivessel coronary artery disease with 2 conduits (skeletonized grafts and T grafts).

BACKGROUND: Complete arterial CABG is a surgical option to improve long-term results in the treatment of coronary artery disease (CAD). Harvesting of multiple arterial grafts is commonly associated with prolonged operating times and increased trauma. By use of new operative techniques (skeletonized grafts and the T-graft approach), CABG in multivessel CAD is now possible with only 2 grafts. We present our experience in the use of these techniques on a routine basis. METHODS AND RESULTS: Between March 1996 and September 1999, 490 patients (aged 61+/-9 years, 20% female) underwent complete arterial CABG. Left ventricular ejection fraction ranged from 15% to 85% (mean 59+/-15%). Triple-vessel disease was present in 88% of the patients. The incidence of diabetes mellitus was 32% (14% insulin dependent). Either both internal thoracic arteries (ITAs) (23%) or the left ITA and radial artery (77%) were used as conduits. In 85% of the patients, a T graft was created. Mean operating time was 198+/-46 minutes; bypass time, 82+/-25 minutes; and ischemic time, 58+/-22 minutes. Two to 7 (mean 4.1+/-0.9) anastomoses were performed per patient. Perioperative intra-aortic balloon pump was necessary in 12 patients (2.4%). The rate of perioperative myocardial infarction was 1.2%. Sternal complications occurred in 1. 0%, and in-hospital mortality was 2.2%. Postoperative coronary angiography in 172 patients (35%) documented excellent patency rates (left ITA 98.3%, right ITA 96.5%, and radial artery 96.6%). CONCLUSIONS: Complete arterial revascularization in multivessel CAD is possible with the use of only 2 grafts with good perioperative results. This approach allows for complete arterial CABG on a routine basis.

Effects of hematocrit on cerebral microcirculation and tissue oxygenation during deep hypothermic bypass.

BACKGROUND: One rationale for hemodilution during hypothermic cardiopulmonary bypass (CPB) has been improved microcirculation. However, the optimal degree of hemodilution remains unclear. We therefore studied cerebral microcirculation and tissue oxygenation in a new intravital microscopic model at 3 different hematocrit (Hct) values. METHODS AND RESULTS: Three groups of 5 piglets with a cranial window over the parietal cortex underwent cooling at Hct of 10%, 20%, or 30%, followed by 1-hour deep hypothermic circulatory arrest (DHCA) and rewarming on CPB. For assessment of functional capillary density (FCD), plasma was labeled with fluorescein-isothiocyanate-dextran. Rhodamine-stained leukocytes were observed in postcapillary venules with analysis for adhesion and rolling. NADH, a natural intracellular fluorophore that increases during ischemia, was measured densitometrically during bypass and DHCA. FCD did not significantly differ from baseline during cooling in any group. However, during early reperfusion (5 minutes) after DHCA, the FCD was significantly higher in the Hct 30% group than in the Hct 10% group. Leukocyte adherence decreased in all groups during CPB and was only moderately increased at the end of the experiment. However, severe hemodilution (Hct 10%) was associated with a significantly greater number of rolling leukocytes relative to Hct 30%. CONCLUSIONS: Higher Hct does not impair cerebral microcirculation and reduces white cell/endothelial activation after deep hypothermic bypass and circulatory arrest. Severe hemodilution (Hct 10%) results in evidence of inadequate cerebral tissue oxygenation during the cooling phase of CPB. This study suggests that Hct of 30% is preferable relative to lower Hct values during hypothermic CPB, particularly if DHCA is used.

[Cystic lesion of the dorsal mediastinum]. / Zystische Raumforderung im hinteren Mediastinum.

We present the case of a 52-year-old male who underwent thoracotomy for resection of a suspected bronchogenic cyst in the right posterior mediastinum. The size of the tumor had increased over years, according to repeated X-rays, and the cyst became symptomatic with obstruction of the right subclavian and jugular veins. To our surprise, histopathology revealed a hydatid cyst.

A classification of cardiac allograft rejection. A modification of the classification by Billingham.

We herein propose a classification of rejection in cardiac allografts based on the original Stanford work. Our modified classification, as a work hypothesis, defines the following grades: mild acute rejection (A-1), corresponding to Billingham's "mild rejection"; mild acute rejection with probable conversion to moderate rejection (A-2); moderate acute rejection (A-3), comparable to Billingham's "moderate rejection"; and severe acute rejection (A-4), morphologically identical with the respective grade in the Billingham classification. The resolution of rejection has been classified into two grades--early (A-5a) and late (A-5b) resolution--according to the development of granulation tissues. We also grade the degree of vasculopathy (B-1, B-2) and chronic rejection (C), which is characterized by aggressive fibrosis and persistent vasculopathy. Mild rejection with possible conversion to moderate rejection is defined by an increasing quantity of retrogressive changes in myocytes. Changes not related to transplantation are characterized in our classification by descriptive diagnosis. The proposed classification was validated by 1 year of clinical experience and by the evaluation of possible prognostic aspects of the classification.

The importance of static lung inflation during organ storage: the impact of varying ischemic intervals in a double lung rat transplantation model.

To determine the importance of static lung inflation during storage, graft performance was evaluated at different levels of intratracheal pressure and varying ischemic intervals. Lewis rat lungs were perfused with low-potassium Euro-Collins and stored for 4 or 8 hr either in atelectasis (4 hr: group I; 8 hr: group IV, respectively) or 13 (group II; V) or 26 cmH2O of airway pressure (groups III, VI). Following implantation continuous measurement of alveolar-arterial oxygen difference (AaDO2*) and pulmonary vascular resistance (PVR) were performed. Separate ventilation allowed assessment of mechanical lung function of the graft. At the end of reperfusion (120 min) weight gain, histology, and phospholipid and protein content in the pulmonary lavage were compared between the groups. Despite significant differences in survival at 4 hr of ischemia graft function did not differ in groups I to III. In contrast, static inflation had a significant impact after 8 hr of ischemia. Lungs stored in atelectasis (group IV) could not be reperfused and failed immediately. Survival in group V was 83+/-11 versus 107+/-7 min in group VI (P<0.05). Compliance at 80 min was 27+/-3 in group V and 52+/-6 ml/cmH2O in group VI (P<0.02). Corresponding values for PVR were 232+/-92 and 112+/-16 mmHg/ml/min, respectively (P<0.05). Less inflation and longer ischemia resulted in a reduction of the large to small phospholipid aggregate ratio and deterioration of surfactant function in the bubble surfactometer. In conclusion, while the amount of static lung inflation may not be critical following short ischemia, the performance of the graft improves significantly with full inflation (26 cmH2O) following extended ischemia (8 hr).

Antitachycardia pacing in patients with implantable cardioverter-defibrillators: inverse circadian variation of therapy success and acceleration.

We analyzed spontaneous ventricular tachycardias treated by antitachycardia pacing during long-term follow-up in 138 recipients of an implantable cardioverter-defibrillator. An inverse circadian variation of the antitachycardia pacing termination and acceleration rates with the worst antitachycardia pacing success during the time period with the highest episode frequency (morning hours) was demonstrated.

Cortisol, corticotropin, and beta-endorphin responses to corticotropin-releasing hormone in patients with atopic eczema.

Alterations in the hypothalamic-pituitary-adrenal (HPA) system are well documented in affective disorders. In depression these include increased secretion of cortisol, an insufficient suppressibility of cortisol by dexamethasone, a blunted corticotropin (ACTH) response to corticotropin-releasing hormone (CRH) and a dysfunction of the glucocorticoid receptor. Patients with atopic eczema, a common chronic skin disease, show seasonal variations in disease activity, symptoms of minor depression and immunological disturbances similar to those seen in patients with depression. To explore the integrity of the HPA system integrity in individuals with atopic eczema we studied the 24-h cortisol secretion and the cortisol, ACTH and beta-endorphin responses to CRH in such individuals and in healthy controls matched for sex and age. The 24-h secretion of cortisol did not differ between the patients with atopic eczema and the controls. The net response to CRH administered as a 100 micrograms i.v. bolus was significantly attenuated for both cortisol (24,235 +/- 12,443 vs. 47,019 +/- 34,515 nmol.min/dl; p < .03) and for ACTH (546 +/- 205 vs. 727 +/- 310 pmol.min/l; p < .05) in the patient group, whereas the beta-endorphin response did not differ between the groups (1072 +/- 448 vs. 1603 +/- 421 nmol.min/l). The blunted response of cortisol and ACTH cannot be explained by hypercortisolism as it is the case in major depression. Rather, it may be related to a prolonged underexposure to hypothalamic CRH or to an increased sensitivity of glucocorticoid feedback inhibition.

Decreased expression of the cystic fibrosis transmembrane conductance regulator protein in remodeled airway epithelium from lung transplanted patients.

The absence or mislocalization of cystic fibrosis transmembrane conductance regulator (CFTR) is regarded as being specific for cystic fibrosis (CF). In principle, the supply of a non-CF lung transplant to a CF patient should bring up normal CFTR expression in the lower airways. Immunolocalization of CFTR and of epithelial differentiation markers (ie, cytokeratins 13, 14, and 18, and desmoplakins 1 and 2) was carried out on 21 mucosal biopsies from the upper lobe of grafts in non-CF (n = 12) and CF patients (n = 9) retrieved between days 23 and 1,608 after lung transplantation. Biopsy specimens from seven non-CF and four CF patients presented either a pseudostratified respiratory epithelium or slight basal cell hyperplasia. CFTR was distributed at the apical membrane of the ciliated cells. In remodeled epithelia with basal cell hyperplasia or squamous metaplasia, CFTR was either weakly expressed in the cytoplasm of the superficial epithelial cells or was undetectable. The extent of epithelium remodeling was significantly correlated with an impairment of lung function. The results suggest that posttransplant airway epithelium dedifferentiation of the graft leads to the loss of properly targeted CFTR irrespective of the underlying disease of the recipient.

The prevalence and management of bronchial anastomotic complications in lung transplantation.

The prevalence and management of bronchial anastomosis complications have been assessed in a series of 53 patients undergoing lung transplantation. Of the 50 patients subsequently at risk of airway complications, these problems occurred in seven (14%). Only one patient died as a direct result of the airway complication (2%). Four patients required airway stenting, and their management is discussed. Although airway healing is normal in the majority of patients undergoing lung transplantation (86%), when deficits occur they can usually be successfully managed with conservative treatment. Bronchial stenting may be required on either a temporary or a permanent basis.