Variation of Donor and Acceptor Strength in Analogues of Brooker's Merocyanine and Generalization to Various Classes of Charge Transfer Compounds.

Derivatives of Brooker's merocyanine (BM) have been investigated, which possess different donors and acceptors and therefore vary their donor-acceptor strength SDA. The 00 energies have been extracted from the spectra and compared. Under basic conditions, where the neutral (merocyanine) form is present, the absorption energies for all compounds are similar, whereas there is a large difference for acidic conditions where the cationic (cyanine) form is present. This behavior could be explained by a simple theoretical model involving the dependence of the excitation energy Δ E01 on SDA. This model can be generalized to describe in a consistent way two different well-known classes of neutral chromophores with a certain degree of charge separation, namely merocyanine I (TICT) and merocyanine II (often betainic) compounds. Merocyanines I are characterized by a medium polar aromatic ground state and a zwitterionic quinoid excited state and hence positive solvatochromism, whereas merocyanines II are formally characterized by a zwitterionic aromatic ground state and a less polar quinoid excited state and, accordingly, by negative solvatochromism. On increasing the donor-acceptor strength SDA sufficiently, merocyanines II can, however, move to the so-called overcritical region with the excited state dominated by the zwitterionic valence bond structure. For many of the merocyanine II molecules investigated here, a weakly positive solvatochromic behavior is observed indicating that the ground state contains less of the zwitterionic valence bond wave function than the excited state and that these compounds belong to the overcritical region. The fluorescence spectra have been analyzed in terms of the Franck-Condon model and confirm these conclusions.

Is denial a maladaptive coping mechanism which prolongs pre-hospital delay in patients with ST-segment elevation myocardial infarction?

OBJECTIVE: During an acute myocardial infarction, patients often use denial as a coping mechanism which may provide positive mood regulating effects but may also prolong prehospital delay time (PHD). However, empirical evidences are still sparse. METHODS: This cross-sectional study included 533 ST-elevated myocardial infarction (STEMI) patients from the Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Data on sociodemographic, clinical and psycho-behavioral characteristics were collected at bedside. The outcome was assessed using the Cardiac Denial of Impact Scale (CDIS) with the median split as cutoff point. A total of 206 (41.8%) STEMI patients were thus classified as deniers. RESULTS: Deniers were less likely to suffer from major depression (p=0.04), anxiety (p=0.01) and suboptimal well-being (p=0.01) compared to non-deniers during the last six months prior to STEMI. During STEMI, they were less likely to perceive severe pain strength (p=0.04) and racing heart (p=0.02). Male deniers were also less likely to perceive shortness of breath (p=0.03) and vomiting (p=0.01). Denial was not associated with overall delay time. However, in the time window of 3 to 24h, denial accounted for roughly 40min extra delay (356 vs. 316.5min p=0.02 n=196). CONCLUSIONS: Denial not only contributes to less suffering from acute heart related symptoms and negative affectivity but also leads to a clinically significant delay in the prevalent group.

Frequency and covariates of fear of death during myocardial infarction and its impact on prehospital delay: findings from the multicentre MEDEA Study.

BACKGROUND: Fear of death (FoD) is an exceptionally stressful symptom of ST-elevation myocardial infarction (STEMI), which received little scientific attention in recent years. We aimed to describe the prevalence and factors contributing to FoD among STEMI patients and assess the impact of FoD on prehospital delay. METHODS: This investigation was based on 592 STEMI patients who participated in the Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Data on sociodemographic, clinical and psycho-behavioral characteristics were collected at bedside. Multivariate logistic regression models were used to identify factors associated with FoD. RESULTS: A total of 15% of STEMI patients reported FoD (n = 88), no significant gender difference was found. STEMI pain strength [OR = 2.3 (1.4-3.9)], STEMI symptom severity [OR = 3.7 (2-6.8)], risk perception pre-STEMI [OR = 1.9 (1.2-3.2)] and negative affectivity [OR = 1.9 (1.2-3.1)] were independently associated with FoD. The median delay for those who experienced FoD was 139 min compared to 218 min for those who did not (p = 0.005). Male patients with FoD were significantly more likely to delay less than 120 min [OR = 2.11(1.25-3.57); p = 0.005], whereas in women, this association was not significant. Additionally, a clear dose-response relationship between fear severity and delay was observed. Male FoD patients significantly more often used emergency services to reach the hospital (p = 0.003). CONCLUSIONS: FoD is experienced by a clinically meaningful minority of vulnerable STEMI patients and is strongly associated with shorter delay times in men but not in women. Patients' uses of emergency services play an important role in reducing the delay in male FoD patients.

Sex specific impact of prodromal chest pain on pre-hospital delay time during an acute myocardial infarction: Findings from the multicenter MEDEA Study with 619 STEMI patients.

BACKGROUND: Scarce evidence yields conflicting results regarding the effect of prodromal chest pain (PCP) on pre-hospital delay during an acute myocardial infarction (AMI). We aimed to assess the impact of PCP on delay. METHODS: Data was collected on 619 ST-elevated MI patients from the multicenter Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Patients with any PCP (which was subdivided into undefined PCP, possible and definite angina) within a year before AMI were identified using the Rose questionnaire, administered in bedside interviews. The influence of PCP and its subdivisions (all compared to no PCP) was assessed using logistic regression (with cut-offs of 2 h, 6 h, and a 4-category ordinal outcome). RESULTS: Any type of PCP was reported by men (50.6%) more than women (34.6%) (OR=1.9; 95% CI: 1.3 to 2.8; p=.001). The median delay of patients with PCP was not significantly different to delay in patients with no PCP (p=.327). Prolonged delay times were observed in women with PCPs of lesser degree of cardiac confirmation, while the opposite was observed in men. In women, possible angina was more strongly associated with delay <2 h (OR=6.8; 95% CI=2 to 23.8) than any PCP (OR=2.6; 95% CI=1.2 to 5.7). CONCLUSIONS: For men, PCPs of increasing cardiac confirmation are associated with prolonged delay. For women, PCPs of lesser cardiac confirmation are more likely to lead to prolonged delay. Future studies should investigate mediating factors.

Classification of skin sensitizing substances: a comparison between approaches used by the DFG-MAK Commission and the European Union legislation.

A systematic classification of substances (or mixtures of substances) with regard to various toxicological endpoints is a prerequisite for the implementation of occupational safety strategies. As its principal task the "Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area" of the "Deutsche Forschungsgemeinschaft" (DFG-MAK Commission) derives and recommends maximum workplace concentrations and biological tolerance values (MAK and BAT values) based exclusively on scientific arguments. Several endpoints are evaluated separately in detail, e.g. carcinogenicity, risks during pregnancy, germ cell mutagenicity or contribution to systemic toxicity after cutaneous absorption. Skin- and airway sensitization is also considered; the present paper focuses on these two endpoints.

Responses to iron limitation in Hordeum vulgare L. as affected by the atmospheric CO2 concentration.

Elevated atmospheric CO2 treatments stimulated biomass production in Fe-sufficient and Fe-deficient barley plants, both in hydroponics and in soil culture. Root/shoot biomass ratio was increased in severely Fe-deficient plants grown in hydroponics but not under moderate Fe limitation in soil culture. Significantly increased biomass production in high CO2 treatments, even under severe Fe deficiency in hydroponic culture, indicates an improved internal Fe utilization. Iron deficiency-induced secretion of PS in 0.5 to 2.5 cm sub-apical root zones was increased by 74% in response to elevated CO2 treatments of barley plants in hydroponics but no PS were detectable in root exudates collected from soil-grown plants. This may be attributed to suppression of PS release by internal Fe concentrations above the critical level for Fe deficiency, determined at final harvest for soil-grown barley plants, even without additional Fe supply. However, extremely low concentrations of easily plant-available Fe in the investigated soil and low Fe seed reserves suggest a contribution of PS-mediated Fe mobilization from sparingly soluble Fe sources to Fe acquisition of the soil-grown barley plants during the preceding culture period. Higher Fe contents in shoots (+52%) of plants grown in soil culture without Fe supply under elevated atmospheric CO2 concentrations may indicate an increased efficiency for Fe acquisition. No significant influence on diversity and function of rhizosphere-bacterial communities was detectable in the outer rhizosphere soil (0-3 mm distance from the root surface) by DGGE of 16S rRNA gene fragments and analysis of marker enzyme activities for C-, N-, and P-cycles.

Construction of phage display libraries from reactive lymph nodes of breast carcinoma patients and selection for specifically binding human single chain Fv on cell lines.

The display of recombinant antibody fragments on the surface of filamentous phage mimicks B cells and is therefore a technology ideal to generate antibodies against any potential target antigen in vitro. In order to obtain tumor specific, high-affinity single chain antibody fragments (scFv), it has been speculated that lymph node tissue from cancer patients infiltrated with activated B cells must be a valuable source of antibody V-genes. The aim of this study was to generate a human scFv-phage library from lymph nodes of patients with breast cancer and to develop a stringent depletion and selection protocol in order to isolate specific single chain antibodies recognizing potentially new antigens in breast cancer. The amplification of the V-genes cloned from regional lymph node tissue and their assembly to single chain variable fragments was optimized in terms of library size and diversity. A large set of degenerated primers, annealing to all known V-gene families, was designed and used under optimized PCR conditions. The amplified V-genes were genetically fused in all possible combinations and cloned into a phagemid vector. Depletion and selection on mammary epithelial and primary breast carcinoma cell lines, respectively led to the isolation of a breast cancer cell line specific scFv (BCK-1 scFv) from this patient-derived scFv-phage display library as demonstrated in polyclonal and monoclonal ELISA, using immobilized cell membrane fractions of the indicated cell lines. A new recombinant breast cancer cell line specific antibody based on V-genes derived from reactive B-lymphocyte-infiltrated lymph nodes of patients with breast cancer was isolated via phage display, performing stringent depletion and selection protocols. We believe that this combination of antibody V-gene source and elaborated phage display depletion and selection strategy will be successful for the retrieval of numerous other recombinant, tumor specific antibody fragments.

Combination therapy of disseminated Fusarium oxysporum infection with terbinafine and amphotericin B.

A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality.

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.

Oral immunisation of wild boar against classical swine fever: concluding analysis of the recent field trials in Germany.

The recent oral immunisation trials in wild boar against classical swine fever (CSF) in Germany are described and evaluated in summary. After the first field study in Lower Saxony from 1993-1995 further immunisation trials started in Mecklenburg-Western Pomerania, Brandenburg, Lower Saxony, Baden-Württemberg and Saxony-Anhalt. The immunisation strategies and the size of the vaccination zones were different in the individual federal states. In principle, the bait vaccine based on the CSF virus strain "C" were laid out by hand. Later also the aerial distribution was carried out in selected areas of Mecklenburg-Western Pomerania. The application of baits by plane was introduced at the beginning of the immunisation measures in Saxony-Anhalt apart from the manual distribution. Up to now, the field trials show that the oral immunisation can be an additional tool for CSF control by increasing of herd immunity and reduction of the CSFV prevalence. However, the immunisation was not sufficient enough for young boars in the most field studies. Based on the evaluation of the immunisation experiments an improved immunisation procedure is recommended.

Apical to basolateral transcytosis and apical recycling of immunoglobulin G in trophoblast-derived BeWo cells: effects of low temperature, nocodazole, and cytochalasin D.

The murine neonatal Fc receptor, FcRn, carries out two functions: materno-fetal IgG delivery and maintenance of serum IgG homeostasis. During human pregnancy maternal IgG is transferred across placental syncytiotrophoblasts presumably by the human homolog of FcRn, hFcRn. Trophoblast-derived BeWo cells express hFcRn endogenously and can be considered as a model system to investigate IgG transport in syncytiotrophoblasts. Using a pulse-chase protocol, we here demonstrate that polarized BeWo cells exhibit not only apical to basolateral transcytosis but also apical IgG recycling. Thus, for the first time we demonstrate that epithelial cells can be involved in both materno-fetal IgG transmission and regulation of serum IgG levels. Lowering the temperature from 37 to 16 degrees C reduced, but did not block, IgG recycling and transcytosis. Microtubule-disruption by nocodazole did not influence transcytosis or apical recycling. Disassembly of filamentous actin by cytochalasin D stimulated apical endocytosis and recycling, while transcytosis remained unaffected. In summary, in BeWo cells apically internalized IgG enters both a transcytotic and recycling pathway. While the transcytotic route is temperature-sensitive but independent from microtubules and actin filaments, the apical recycling pathway is temperature-influenced and stimulated by actin disassembly, suggestive for the involvement of distinct endosome subcompartments in transcytosis and recycling.

Attitudes toward hearing-impaired children in less developed countries: a pilot study.

Various anecdotal reports have been presented about attitudes to hearing loss and deafness in less developed countries but few studies have addressed this matter systematically. In the present study, we have applied a standardised questionnaire to 357 teachers from as uniform a sample as possible within 20 countries in Africa, Latin America, and Asia and compared the results with those obtained from 107 teachers in Western Europe. The questions tapped into their responses toward developing hearing loss themselves, hearing loss in children they encountered. and which group of children with disabilities they would prefer to teach. The geographical origins of the teachers influenced all measures except their view of the contribution that deaf children could make to society. This was influenced solely by the age of the responding teacher.

Changes of the hemostatic network in critically ill patients--is there a difference between sepsis, trauma, and neurosurgery patients?

OBJECTIVE: To study the time course of coagulation data in intensive care patients. DESIGN: Prospective, descriptive study. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit of a university hospital. PATIENTS: Fifteen patients with severe trauma (injury severity score, 15 to 25), 15 sepsis patients secondary to major surgery, and 15 neurosurgery patients (cancer surgery) were studied. INTERVENTIONS: Standardized intensive care therapy. MEASUREMENTS AND MAIN RESULTS: Standard coagulation data and molecular markers of coagulation activation and fibrinolytic activity (soluble thrombomodulin, protein C, free protein S, thrombin/antithrombin III complex, plasmin-alpha 2-antiplasmin complex, tissue plasminogen activator, platelet factor 4, beta-thromboglobulin were measured from arterial blood samples on the day of admission to the intensive care unit (trauma/neurosurgery patients) or on the day of diagnosis of sepsis (baseline value) and serially during the next 5 days. Antithrombin III, fibrinogen, and platelet counts were highest in neurosurgery patients but without significant differences between sepsis and trauma patients. Thrombin/antithrombin III complex increased in the sepsis patients (from 22.6+/-4.2 microg/L to 39.9+/-6.8 microg/L), but decreased in trauma (from 40.2+/-5.1 microg/L to 17.6+/-4.0 microg/L) and neurosurgery patients (from 28.2+/-4.2 microg/L to 16.2+/-3.8 microg/L). Tissue plasminogen activator increased in the sepsis patients (from 14.4+/-3.9 microg/L to 20.7+/-3.8 microg/mL) and remained almost unchanged in the other two groups. Soluble thrombomodulin plasma concentration increased significantly in the sepsis group (max, 131.8+/-22.5 ng/mL), while it remained elevated in the trauma (max, 75.5+/-5.9 ng/mL) and was almost normal in the neurosurgery patients. Protein C and free protein S remained decreased only in the sepsis group. CONCLUSIONS: Alterations of the hemostatic network were seen in all three groups of critically ill patients. Hemostasis normalized in the neurosurgery patients and posttraumatic hypercoagulability recovered within the study period. By contrast, monitoring of molecular markers of the coagulation process demonstrated abnormal hemostasis in the sepsis patients during the entire study period indicating ongoing coagulation disorders and abnormalities in fibrinolysis in these patients.

Continuous heparinization and circulating adhesion molecules in the critically ill.

Endothelial activation and damage are common endpoints of a complex process that may result in multiple organ dysfunction syndrome (MODS). The influence of continuous intravenous heparinization on plasma levels of circulating adhesion molecules was studied in 28 trauma patients (injury severity score between 15 and 25 points) and 28 sepsis patients secondary to abdominal surgery. According to a prospective, randomized sequence the patients received either unfractionated heparin (aim: activated partial thromboplastin time (aPTT) approximately 2 x normal) (trauma-heparin (n = 14); sepsis-heparin (n = 14)) or not (trauma (n = 14); sepsis (n = 14)). Plasma levels of circulating soluble endothelial leukocyte adhesion molecule-1 (sELAM-1), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (slCAM-1), and granule membrane protein-140 (sGMP-140) were serially measured from arterial blood samples for 5 days. Approximately 600 U/h of heparin were given to increase aPTT to approximately 60 s. Plasma levels of all adhesion molecules increased in all groups. This increase was significantly (p < .05) highest in both sepsis groups (sepsis: sELAM-1: from 50+/-11 to 84+/-19 ng/mL; slCAM-1: 410+/-68 to 700+/-95 ng/mL), but did not differ significantly between the treated and nontreated patients (sepsis-heparin: sELAM-1: from 60+/-131 to 88+/-20 ng/mL; slCAM-1: from 398+/-99 to 686+/-119 ng/mL). Trauma patients showed a less pronounced increase in all adhesion molecules without differences between the two subgroups. Only sGMP-140 increased significantly (p < .05) more in the trauma (from 102+/-20 to 169+/-16 ng/mL) than in the trauma-heparin group (from 109+/-19 to 132+/-17 ng/mL). It is summarized that continuous heparinization with approximately 600 U/h did not attenuate the rise in circulating adhesion molecules in sepsis and trauma patients. The study findings suggest that heparin in this dose regimen may be unlikely to influence endothelial inflammation or endothelial function in critically ill patients.

Development of a narrow water-immersion objective for laserinterferometric and electrophysiological applications in cell biology.

Laserinterferometric studies of the micromechanical properties of the organ of Corti using isolated temporal bone preparations are well established. However, there are relatively few measurements under in vivo conditions in the apical region of the cochlea because of its inaccessibility with commonly used techniques. Recently, optical-design programs have become affordable and powerful, so that the development of an optimized optical system is within the budget of physiologists and biophysicists. We describe here the development of a long-range water-immersion objective. To circumvent anatomical constraints, it has a narrow conical tip of taper 22 degrees and diameter 2.4 mm. It is a bright-field reflected-light illumination, achromatic objective with magnification of 25x/infinity, a working distance of 2.180 mm and a numerical aperture of 0.45. Chromatic errors are corrected at 546.1 and 632.8 nm, with emphasis on the latter wavelength which is used by the laser interferometer. The field curvature is relatively flat and a diffraction limitation (Strehl ratio better than 0.8) can be obtained in a field of 0.4 mm diameter. Using this objective, sound-induced vibrations of hair cells and Hensen cells could be recorded without placing a reflector on the target area. In addition, this objective was found to be diffraction-limited in the near infra-red (750-830 nm), with a slightly different working distance (2.186 mm), making it suitable for patch-clamp experiments using infra-red, differential interference contrast.

Does continuous heparinization influence platelet function in the intensive care patient?

OBJECTIVE: To study the influence of continuous administration of heparin on platelet function in intensive care patients. DESIGN: Prospective, serial investigation. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. PATIENTS: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. INTERVENTIONS: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). MEASUREMENTS AND RESULTS: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 mumol/l), collagen (10 micrograms/ml), and epinephrine (25 mumol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4-10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e.g., epinephrine-induced maximum platelet aggregation:-45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e.g., ADP-induced maximum platelet aggregation: +42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. CONCLUSIONS: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient.

Dual-wavelength heterodyne differential interferometer for high-precision measurements of reflective aspherical surfaces and step heights.

A dual-wavelength heterodyne differential interferometer was developed and tested together with scanning mechanics. To extend the range of unambiguity, two wavelengths were applied. This is important for measuring structures with surface discontinuities (reliefs, steps). The automatic adjustment of the interferometer with respect to the rotational symmetrical measuring surfaces (aspheres) is important. An adjustment is needed to scan the asphere through its vertex. Typical measurements on a sphere, an asphere, and steps are shown.