Probe of Multielectron Dynamics in Xenon by Caustics in High-Order Harmonic Generation.

We investigated the giant resonance in xenon by high-order harmonic generation spectroscopy driven by a two-color field. The addition of a nonperturbative second harmonic component parallel to the driving field breaks the symmetry between neighboring subcycles resulting in the appearance of spectral caustics at two distinct cutoff energies. By controlling the phase delay between the two color components it is possible to tailor the harmonic emission in order to amplify and isolate the spectral feature of interest. In this Letter we demonstrate how this control scheme can be used to investigate the role of electron correlations that give birth to the giant resonance in xenon. The collective excitations of the giant dipole resonance in xenon combined with the spectral manipulation associated with the two-color driving field allow us to see features that are normally not accessible and to obtain a good agreement between the experimental results and the theoretical predictions.

Pulmonary hypertension in HIV infection: a prospective echocardiographic study.

OBJECTIVES: While idiopathic pulmonary arterial hypertension (PAH) is a rare disease, it is seen more frequently in patients with HIV infection. The aim of this study was to evaluate the prevalence of pulmonary hypertension (PH) in patients with HIV infection by echocardiographic screening. METHODS: Echocardiography and N-terminal of the prohormone brain natriuretic peptide measurement were used to examine the prevalence of PH prospectively in HIV-positive patients (n = 374) during routine follow-up visits for HIV disease. RESULTS: In echocardiographic screening, PH was detected in a total of 23 of 374 HIV-infected patients (6.1%). Of these, three patients (13%) presented with symptoms of dyspnoea and fatigue, and diagnosis of PAH was confirmed by right heart catheterization. Patients with systolic pulmonary artery pressure (sPAP) > 30 mmHg were more likely to be female, to have a history of injecting drug use and to originate from high-prevalence countries (HPCs). CONCLUSIONS: Echocardiographic screening detected PH in a substantial proportion of HIV-positive patients. Female gender, a history of injecting drug use and HPC origin were associated with a higher prevalence of HIV-associated PH. The relevance and long-term outcome of these findings need to be validated in follow-up studies, which are ongoing.

[Cardiac sarcoidosis: diagnostic and therapeutic algorithms]. / Diagnostik und Therapie der kardialen Sarkoidose.

Sarcoidosis is a multisystemic granulomatous disorder which affects the respiratory system in the majority of the cases. Cardiac manifestations are found in up to 10 % of the affected cohort and show a large heterogeneity based on the ethnic background. Cardiac sarcoidosis are not only found in patients with rhythmogenic heart disease such as atrial and ventricular fibrillation but also in all phenotypes of cardiomyopathies. The overall morbidity and mortality caused by cardiac sarcoidois in Germany is unclear and no large prospective international studies are published on this topic. This consensus paper on diagnostic and therapeutic algorithms in cardiac sarcoidosis is based on a current literature search and forms a expert opinion statement under the hospices of the "Deutsche Gesellschaft für Pneumologie" and "Deutsche Gesellschaft für Kardiologie". It is the rationale of this statement to offer algorithms to facilitate clinical decision-making based on the individual case.

Transforming growth factor-{beta} gene polymorphisms in different phenotypes of sarcoidosis.

The aetiology of sarcoidosis is unclear. Single nucleotide polymorphisms (SNPs) in transforming growth factor (TGF)-ß2 and -ß3 have been reported to be associated with the development of lung fibrosis in patients with sarcoidosis. SNPs in TGF-ß2 (rs1891467) and TGF-ß3 (rs3917200) were investigated in 296 patients with sarcoidosis (acute/self remitting, n = 70 (including 62 patients with Löfgren's syndrome); chronic, n = 168; acute/chronic, n = 58) by real-time PCR. 32 patients showed radiological signs of lung fibrosis. The genotype frequencies were compared among the sarcoidosis groups as well as to 377 healthy controls. We found a significant association with the G-allele in rs1891467 in TGF-ß2 and an acute/self remitting course of sarcoidosis compared to a chronic course (p = 0.001). The results were even more evident for patients with Löfgren's syndrome (p<0.001). Moreover, we could demonstrate a borderline significance between TGF-ß3 (rs3917200) and lung fibrosis (p = 0.050). Carriers of the G-allele in rs1891467 might be protected from developing a chronic course. Moreover, there is evidence that rs3917200 is involved in the development of lung fibrosis in sarcoidosis. This study is the first in sarcoidosis patients to suggest a genetic implication of TGF-ß2 as a protective factor in the course of sarcoidosis.

Caspase recruitment domain 15 gene haplotypes in sarcoidosis.

Sarcoidosis is a systematic granulomatous disorder. Genetic susceptibility could play a central role in the disease development and progression. In this study, we investigated whether caspase recruitment domain 15 (CARD15) gene haplotypes are associated with the onset or the clinical course of sarcoidosis. Three hundred Caucasian sarcoidosis patients and 381 matched controls were included. Eight haplotype-tagging single nucleotide polymorphisms (SNPs) in the CARD15 gene were examined by mass spectrometry-based SNP genotyping. By haplotype analysis, mutations located in between tested SNPs can also be identified. Therefore, we can conclude that there is no association between the CARD15 gene and the development or a special phenotype of sarcoidosis in our cohort.

Improvement of quality of life in patients with concomitant allergic asthma and atopic dermatitis: one year follow-up of omalizumab therapy.

OBJECTIVE: Anti IgE treatment with omalizumab is efficacious in the treatment of patients suffering from allergic asthma, improving asthma control and improving quality of life. Furthermore, this approach could be beneficial for patients with concomitant atopic dermatitis. We assessed quality of life and asthma control in atopic patients with allergic asthma and concomitant atopic dermatitis versus those with asthma and without atopic dermatitis treated with omalizumab. - METHODS: A total of 22 patients with severe allergic asthma were treated with omalizumab for 12 months. 13 patients with allergic asthma without concomitant atopic dermatitis (IgE 212 ± 224 IU/ml) and 9 patients with concomitant allergic asthma and atopic dermatitis (IgE 3,528 ± 2,723 IU/ml) were included. Asthma-related quality of life (AQLQ), atopic dermatitis related quality of life (DLQI), and asthma-related treatment were compared between both groups at baseline and after initiating omalizumab treatment. - RESULTS: DLQI was significantly in favor of omalizumab after 2 months in the atopic dermatitis/asthma group (P = 0.01); AQLQ was improved after 6 months in the asthma group (P = 0.01), while no change was seen in AQLQ in the atopic dermatitis/asthma group (P = 0.12). Omalizumab controlled oral corticosteroid use more effective (P<0.01) in patients with asthma and atopic dermatitis (in 9/9 cases) compared to patients with asthma alone (9/13). Baseline IgE as well as other factors do not predict response to omalizumab. - CONCLUSIONS: Omalizumab is effective in improving atopic dermatitis-related quality of life scores and modulates oral corticosteroid use in patients with concomitant asthma and atopic dermatitis in a positive fashion.

Extended genetic analysis of BTNL2 in sarcoidosis.

Single nucleotide polymorphisms in the BTLN2 gene have been recently associated with the risk for sarcoidosis. We now aimed to study additional genetic alterations in BTLN2 as putative genetic risk. The CNV_ID 507, which was highlighted for its possible involvement in sarcoidosis because of its partly deletion of the BTNL2 gene, was tested for association in a cohort of 89 sarcoidosis patients and 89 matched controls, but our results indicated that CNV_ID 507 does not affect the genomic structure of BTLN2 as previously described. Additionally, we identified a heterozygous 1 bp deletion in exon 3, c.450delC. We genotyped 210 patients and 201 controls for c.450delC and observed similar genotype frequencies in both groups without a significant difference (P = 0.4996).

Angiotensin-converting enzyme I/D polymorphism in chronic obstructive pulmonary disease.

STUDY OBJECTIVE: The etiology of chronic obstructive lung disease (COPD) is unclear. It is supposed to be the product of an exogenous antigenic stimulus, such as tobacco smoke, and an endogenous genetic susceptibility. The angiotensin-converting enzyme (ACE) gene contains a polymorphism based on the presence (insertion [I]) or absence (deletion [D]) of a 287-bp nonsense domain, resulting in three different genotypes (II, ID and DD). The aim of the study was to find out whether the ACE gene polymorphism can determine the course of COPD. PATIENTS AND DESIGN: We genotyped 152 Caucasian patients with COPD and 158 healthy controls for the ACE (I/D) polymorphism. We divided the COPD group into one group of 64 patients with a stable course of disease, defined as less than three hospitalizations over the last three years due to COPD, and another group of 88 patients with an instable course with more than three hospitalizations. RESULTS: The I-allele was significantly associated with an increased risk for COPD in a dominant model (OR 1.67 (95% CI 1.00 to 2.78), p=0.048), but not in a recessive or co-dominant model. Moreover, the I-allele of ACE (I/D) was significantly increased in patients with a stable course of COPD (p=0.012) compared with controls. In a dominant model (II/ID v DD) we found an even stronger association between the I-allele and a stable course of COPD (OR 3.24 (95% CI 1.44 to 7.31), p=0.003). CONCLUSION: These data suggest that the presence of an ACE I-allele determines a stable course of COPD.

ADAM33 gene polymorphisms in chronic obstructive pulmonary disease.

STUDY OBJECTIVE: The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants. Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving. In the present study, we investigated whether single nucleotide polymorphisms in "a disintegrin and metalloprotease" 33 (ADAM33) are associated with the development and course of COPD. PATIENTS AND DESIGN: We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively. To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease. RESULTS: In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively). The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32), in subjects with an unstable course 30.6% (P = 0.47). CONCLUSION: The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD. Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course.

Apparent response to anti-IgE therapy in two patients with refractory "forme fruste" of Churg-Strauss syndrome.

Two cases of formes frustes variants of Churg-Strauss syndrome are reported, who were treated with an antibody against immunoglobulin E as an addition on rescue therapy.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. 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. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

Age-dependent stimulation of neonatal insulin release and inositol phosphate accumulation by CCK-8 and carbachol.

Development of a robust insulin secretory response to glucose occurs during the early neonatal period. To determine if neuroendocrine agents play a role during this time, we studied the effects of selected peptides and neurotransmitters on insulin release and polyphosphoinositide metabolism in islets isolated from 1- and 3-day neonatal rats. Vasoactive intestinal peptide had no effect on glucose-stimulated release in either islet population. In contrast, sulfated cholecystokinin octapeptide (CCK-8) significantly enhanced glucose-induced insulin release in both islet groups. One-day islets were stimulated only by a concentration of 300 nM, whereas 3-day islets were responsive at 3 nM. Similar to CCK-8, there were clear differences in responses to carbachol between 1- and 3-day islets. One-day islets required a concentration of 200 microM for insulin release to be significantly greater than with glucose alone; 3-day islet insulin release was significant at 2 microM carbachol. Both agonists stimulated inositol phosphate accumulation in 3-day islets, but only CCK-8 caused a significant increase over glucose-induced levels in 1-day islets. These results indicate that islet responsiveness to CCK-8 and carbachol develops in parallel during the early neonatal period. This development may be linked to the maturation of a critical step of stimulus-secretion coupling through which these agents act.

Clinical experience with the implantable cardioverter defibrillator.

The implantable cardioverter defibrillator has played an increasingly greater role in the management of episodes of sudden cardiac-related death related to ventricular tachycardia or ventricular fibrillation. This study reviews the cases of 142 patients who underwent insertion of an implantable cardioverter defibrillator, 104 who received a device alone (group I) and 38 who underwent insertion of the device in combination with other cardiac surgical procedures (group II). The overall operative mortality was 3.5% and this did not differ between the two groups. The complication rate was higher for group II than for group I patients, and consisted primarily of an increased incidence of atrial arrhythmias (53% versus 13%; p < 0.001). Late complications included three device infections requiring removal of the defibrillator. The late mortality did not differ between the two groups and was primarily related to congestive heart failure. Sudden cardiac-related death was an uncommon late event, with an actuarial freedom from sudden cardiac-related death of 98%, 97%, and 87% at 1, 2, and 5 years, respectively. The morbidity and mortality rate are low in association with the insertion of an implantable cardioverter defibrillator, even when this is combined with other cardiac surgical procedures. Its insertion is also associated with a low subsequent rate of sudden cardiac-related death.

Food neophobia in childhood affects dietary variety.

OBJECTIVE: To determine whether children with food neophobia (unwillingness to try new foods) have more restrictive diets than children without neophobia. SUBJECTS: Seventy children were classified into 3 groups based on scores obtained on the Food Neophobia Scale: neophobic group, score greater than 41; neophilic group, score less than 27; and average group, score of 28 to 40. DESIGN: Dietary data were collected and analyzed for 3 days selected randomly. The dependent variables measured were energy and nutrient intakes, servings of each Food Guide Pyramid group, and Health Eating Index (HEI) scores. STATISTICAL ANALYSES: chi 2, 1-way analysis of covariance, and Scheffé multiple comparisons tests were conducted. RESULTS: The 3 groups were similar with respect to the number of children meeting two thirds of the RDA/DRI for energy and most nutrients. The exception was vitamin E: fewer neophobic children met two thirds of the recommended value for this nutrient than average and neophilic children. The overall HEI score was significantly lower for the neophobic group compared with the average and neophilic groups. The HEI index showed that children with neophobia had a higher intake of saturated fat and less food variety than children without food neophobia. APPLICATIONS: Dietitians should emphasize increased food variety for children within the context of a healthful diet. Research should be conducted to determine the effects of dietary variety on quality of diet and health of children.

[Acute coronary syndrom as a cardiac manifestation of granulomatosis with polyangiitis]. / Akutes Koronarsyndrom als kardiale Manifestation einer Granulomatose mit Polyangiitis.

HISTORY AND ADMISSION FINDINGS: A 49-year-old patient was admitted to our ward because of a troponin elevation (non ST-elevation myocardial infarction) following a rhinoscopy in an external hospital. The patient complained of typical angina, chronic rhinitis and epistaxis. Analysis of the nasal biopsy had shown the histological finding of granulomatosis with polyangiitis (Wegener's granulomatosis). INVESTIGATION: The consecutively performed catheterization showed a coronary one-vessel disease without significant stenosis. Echocardiography showed diastolic dysfunction as well as hemodynamically not significant pericardial effusion. The MRI scan of the heart revealed multiple myocardial scars located ventricular apical and septal. Extended bilateral pulmonary opacities in the thoracic CT scan, microhematuria, leukocyturia and proteinuria indicated multi-organ involvement of the small vessel disease. TREATMENT AND COURSE: The patient's condition improved quickly in response to steroids and cyclophosphamide, followed by attenuation of clinical symptoms and normalizing blood and renal parameters. CONCLUSION: The prognosis of granulomatosis with polyangiitis is mainly limited by renal and pulmonal involvement. Cardiac involvement is commonly rare and associated with clinical courses refractory to immunosuppressive therapy. Generally, all cardiac structures can be affected, thereby impending serious cardiac events. Normally, granulomatosis with polyangiitis responds quickly to immunosuppressive therapy, associated with a rather good prognosis without higher mortality.

[Acute coronary syndrome as a first manifestation of Churg-Strauss syndrome]. / Akutes Koronarsyndrom als klinische Erstmanifestation einer Churg-Strauss-Vaskulitis.

HISTORY AND ADMISSION FINDINGS: A 53-year-old woman was admitted to our chest pain unit because of an acute coronary syndrome (non ST-elevation myocardial infarction). She complained of asthma, chronic sinusitis and involuntary weight loss, occasional fever and night sweats over the past six months. INVESTIGATIONS: Coronary angiography did not show any signs of macroscopic coronary artery disease, while echocardiography demonstrated a hemodynamically not significant pericardial effusion. Magnetic resonance imaging of the heart revealed a subendocardial scar, extension and localization pointing to a vascular genesis. Thoracic computed tomography revealed pulmonary opacities and blood tests showed an eosinophilia, leading to the clinical diagnosis of Churg-Strauss syndome. TREATMENT AND COURSE: The patient responded quickly to oral steroids, and blood parameters returned to normal. CONCLUSION: Acute coronary syndrome in youngish patients without classical cardiovascular risk factors is suggestive for myocarditis but also for vasculitis. Churg-Strauss syndrome usually responds quickly to immunosuppressive therapy, associated with a rather good prognosis without high mortality.

[Pulmonary hypertension in end-stage renal disease: three case reports]. / Pulmonale Hypertonie bei terminaler Niereninsuffizienz: Drei Kasuistiken.

HISTORY: Within three months, three patients with end-stage renal disease presented for evaluation of pulmonary hypertension (PH): a 72-year-old woman (case 1), a 67-year-old patient (case 2) and a 75-year-old patient (case 3), each with increasing dyspnea (WHO functional class III). INVESTIGATIONS: In all three cases, there was echocardiographic evidence of right heart failure; right heart catheterization was completed before and after dialysis. In case 1, we found a postcapillary PH (PH group 2 - PH with left heart diseases/diastolic dysfunction). Case 2 also showed a postcapillary PH and a high cardiac output of 9.7 l/min. In case 3, unmasked after dialysis, a precapillary, pulmonary arterial hypertension (PAH - group 1) was detected. TREATMENT AND COURSE: In patient 1, no relevant improvement of symptoms was observed, despite optimized cardiac therapy. There was a significant clinical improvement in patient 2 after surgical reduction of the arteriovenous shunt. In patient 3, relevant clinical and hemodynamic improvement was seen under treatment with bosentan. CONCLUSION: These cases confirm the role of right heart catheterization in the differential diagnosis of unclear PH in patients with end-stage renal failure. Moreover, the three cases point to three different causes. Specific therapies can result in significant symptomatic improvement.

Synthesized light transients.

Manipulation of electron dynamics calls for electromagnetic forces that can be confined to and controlled over sub-femtosecond time intervals. Tailored transients of light fields can provide these forces. We report on the generation of subcycle field transients spanning the infrared, visible, and ultraviolet frequency regimes with a 1.5-octave three-channel optical field synthesizer and their attosecond sampling. To demonstrate applicability, we field-ionized krypton atoms within a single wave crest and launched a valence-shell electron wavepacket with a well-defined initial phase. Half-cycle field excitation and attosecond probing revealed fine details of atomic-scale electron motion, such as the instantaneous rate of tunneling, the initial charge distribution of a valence-shell wavepacket, the attosecond dynamic shift (instantaneous ac Stark shift) of its energy levels, and its few-femtosecond coherent oscillations.