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Introduction:Checkpoint inhibitor immunotherapy is associated with numerous adverse events, including eruptive keratoacanthomas and squamous cell carcinomas. However, no cases of immunotherapy-associated verrucous keratoses (VKs) have been reported. VKs are proliferative lesions generally considered benign, although they have been suggested to represent premalignant lesions.Cases:We present the first case series of three patients with immunotherapy-associated VKs. The patients were receiving nivolumab for renal cell carcinoma, combination ipilimumab/nivolumab for non-small cell lung carcinoma, and pembrolizumab for malignant melanoma. The VKs appeared 3-7 months after initiation of immunotherapy. Lesions were treated with shave removal or cryosurgery without recurrence. This report adds to the spectrum of cutaneous squamoproliferative lesions induced by checkpoint inhibitor immunotherapy.

Adult-onset Still’s disease classically presents with high fevers, arthralgias, leukocytosis, and an evanescent eruption. There are, however, a known subset of patients who develop an atypical eruption with persistent erythematous to violaceous papules and plaques. Here, we present the case of a white female in her 40s who presented with 2 years of spiking fevers, arthralgias, and a fixed pruritic eruption with erythematous plaques with overlying scale and linear accentuation. She was initially treated with oral prednisone, anakinra, and methotrexate. Due to persistent symptoms, she was switched to adalimumab with significant relief of symptoms. Prompt recognition of adult-onset Still’s disease with this atypical eruption may help prevent delayed or missed diagnosis and allow for early, appropriate intervention.

Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties (dermatology, oncology, and internal medicine). A 25-question survey was designed to elicit general knowledge and awareness of PCIA, as well as attitudes about referral and treatment. Responses were collected via REDCap, a secure online application, and analyzed with descriptive statistics, chi-square, and ANOVA tests. There was a significant difference in the number of subjects who had heard of PCIA prior to starting the survey (Derm 79%, Onc 30%, IM 22%, p 6 months) than IM (42% and 45% vs. 17%) and significantly more had encountered patients with the condition (47% and 45% vs. 17%). More providers in dermatology and IM knew how to diagnose PCIA compared with oncology (84% and 83% vs. 70%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA, and most providers believed that patients would accept similar types of treatment for PCIA. Dermatology HCPs were more likely to report higher confidence in their abilities to diagnose and manage PCIA than other providers. The results of this survey identify knowledge gaps about PCIA among health care providers. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA as part of survivorship care.

Sclerodermatous graft versus host disease (sclGVHD) is a debilitating complication of hematopoietic stem cell transplant and is characterized by skin thickening and fibrosis that can result in severe contractures. While immunosuppressive therapy remains a mainstay of treatment, the disease course often progresses and, in severe cases, renders patients immobile and wheelchair-bound. Lasers that can target sclerotic lesions to improve tissue pliability and restore range of motion are a promising potential treatment for sclGVHD. Fractional CO2 lasers promote selective collagen remodeling by creating microcolumns of thermal injury that stimulate a wound healing response. Here, we present 2 patients with sclGVHD who underwent treatment with fractional ablative CO2 laser. In this pilot case series demonstrating the novel use of CO2 laser for severe, refractory sclGVHD, two patients were treated with fractional ablative CO2 laser to a focal area of sclerosis. One patient also received clobetasol ointment under occlusion in between treatments. Both patients reported marked subjective improvement in pain and mobility. Objective measurements were recorded for patient 2 who gained roughly 10 degrees of extension and 2 degrees of flexion, as well as a 10% reduction in skin thickness in the treated area. CO2 laser therapy with or without clobetasol ointment under occlusion is a promising treatment modality for sclGVHD.

Sexual and gender minority (SGM) individuals, including lesbian, gay, bisexual, transgender/gender diverse, questioning/queer, intersex, and asexual (LGBTQIA) persons, represent a historically underserved population within the field of medicine, though their unique health needs are increasingly recognized. Part 2 of this two-part review will address unique concerns regarding acne, tanning behavior, sexually transmitted infections, and other health disparities among SGM adolescents. A more comprehensive understanding of the dermatologic needs of SGM youth will better allow pediatric dermatologists to actively and compassionately care for this health disparity population.

Biologic agents such as adalimumab, etanercept, golimumab, certolizumab, ustekinumab, brodalumab, secukinumab, ixekizumab, dupilumab, alefacept, rituximab, omalizumab, tildrakizumab, and guselkumab are now indicated in the treatment of dermatologic disorders. This review reports on current prevention, risk, and management of infection in patients receiving biologic therapy for dermatologic disorders. Although risk of infection in patients receiving biologic agents for management of a dermatologic disorder is well-known, it appears to continue to be a low risk. However, optimal prevention and management of some infection risks remain an unmet need. Although the overall risk for infection during biologic therapy for dermatologic disorders appears to remain low, there remains concern about the level of risk for reactivation of tuberculosis, as well as hepatitis B and C, and the risk for other, often uncommon, serious infection remains unknown. Continued pharmacovigilance serves to mitigate risk as well as promote optimal management of dermatologic disorders with biologic agents.

Background 68Gallium-DOTATATE positron emission tomography–computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with 68Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors. Methods Records of patients who underwent 68Gallium-DOTATATE PET CT from March to December 2017 were prospectively evaluated. The primary endpoint was whether 68Gallium-DOTATATE PET CT changes treatment in patients with neuroendocrine tumors. Descriptive statistics, Fisher exact tests, and nested logistic regressions were conducted. Results A total of 50 consecutive patients were included. Of these, 41 patients (82%) had a biopsy-proven neuroendocrine tumor at the time of imaging. The remaining 9 patients (18%) had symptoms or biochemistry suggestive of a neuroendocrine tumor with negative cross-sectional imaging. 68Gallium-DOTATATE PET CT changed management in 33 patients (66%). There were 24 patients with intermodality changes in management and 9 patients with intramodality changes in management. Patients with scans performed for staging had a higher likelihood of a change in management (P = .006). Conclusion Performing 68Gallium-DOTATATE PET CT should be considered for staging and surveillance of neuroendocrine tumors because it is frequently associated with changes in management.

Physical inactivity has caused serious effects on the health of the population, having an impact on the quality of life and the cost of healthcare for many countries. This has motivated government and private institutions to promote regular physical activity, which, paradoxically, can involve health risks when it is carried out in areas with poor air quality. This review collects information from studies conducted on healthy humans related to the pulmonary effects caused by the practice of physical activity when there is poor air quality. In addition, several challenges related to the technological and educational areas, as well as to applied and basic research, have been identified to facilitate the rational practice of exercise in poor air quality conditions.

Li-Fraumeni syndrome (LFS) is a rare genetic disorder that confers a high risk of developing certain malignancies at a young age. It is caused by germline mutations in the TP53 gene and is typically diagnosed by sequencing this gene in blood cells. The presence of a mutation in approximately half of the DNA reads (allelic fraction of 50%) is an indicator of a germline mutation, such as that in LFS. Clonal hematopoiesis (CH) is an expansion of a hematopoietic clone containing a somatic driver mutation with a low allelic fraction, usually not more than 10% to 20%. This report presents a patient with fallopian tube carcinoma who underwent multigene panel testing for cancer predisposition and was found to have a mutation in the TP53 gene, c.733G>T (p.Gly245Cys). Since the TP53 mutation had an allelic fraction of approximately 50%, it was interpreted as being germline, and the patient was diagnosed as having LFS. A year later, she developed acute myelogenous leukemia. Subsequent mutational analysis showed that the TP53 mutation was absent in her benign tissue sample but present in leukemic cells. Furthermore, sequencing of the fallopian tube tumor tissue revealed a different TP53 gene mutation, c.818G>T (p.Arg273Leu). These observations confirmed that the previously identified mutation in her blood was somatic rather than germline and that she had CH at the time of genetic testing. CH can occasionally lead to a misdiagnosis of a germline mutation and a cancer predisposition syndrome that has significant implications for patients and their families. Therefore, the abnormal result of genetic testing for hereditary cancer susceptibility should be carefully interpreted when the clinical presentation is atypical, when the patient is older, when the gene in question is known to have potential germline and somatic mutations such as the TP53 gene, and when the allelic fraction is approximately 50%.

Checkpoint inhibitor immunotherapy is a transformative treatment for advanced malignancies, but can be associated with numerous immune-related adverse events (irAEs). The majority of irAEs include those that closely resemble known cutaneous and neurocutaneous autoimmune or autoinflammatory diseases, such as scleroderma, psoriasis, and dermatomyositis. We present the case of a 63-year-old man with metastatic melanoma undergoing treatment with nivolumab who developed significant motor weakness, paresthesias of both hands, swollen fingers, and a pruritic rash over the face, chest, and upper back after two cycles. Creatine kinase was elevated. Electromyography revealed a myopathic pattern, muscle biopsy of the deltoid revealed an inflammatory myopathy, and skin biopsy showed interface dermatitis. There were no detectable autoantibodies except positive antinuclear antibody. He was diagnosed with immunotherapy-induced dermatomyositis, nivolumab was held, and he was treated with oral prednisone and intravenous immunoglobulin with overall improvement in myopathic and cutaneous symptoms. Dermatomyositis is an inflammatory myopathy with a characteristic dermatologic presentation that can occur spontaneously, as a paraneoplastic phenomenon, or as a drug reaction. This is the second known case of nivolumab-induced dermatomyositis. A review of the literature revealed seven total cases of immunotherapy-induced dermatomyositis. Functionally disabling autoimmune adverse effects of this severity would frequently persuade providers to discontinue immunotherapy in patients with metastatic disease.

Immune checkpoint inhibitors are used to treat numerous malignancies but may be associated with severe adverse events. Bullous dermatoses, chiefly bullous pemphigoid (BP), are potentially progressive adverse events that cause blistering skin lesions and may involve a significant body surface area. Herein, we report an 87-year-old man with urothelial cell carcinoma undergoing atezolizumab treatment who presented with an acute-onset blistering eruption. Biopsy revealed a subepidermal bulla, direct immunofluorescence revealed linear IgG and C3 deposits at the dermal-epidermal junction, and serum studies revealed elevated levels of antibodies to BP180 and BP230. Anti-PD-L1-induced BP was diagnosed, immunotherapy was withheld, and he was treated with oral doxycycline with niacinamide and clobetasol ointment. He restarted atezolizumab and has successfully received four cycles (every 3 weeks) while continuing this BP treatment regimen. A literature review revealed eight other cases of anti-PD-L1-induced bullous disorders. The incidence of bullous dermatoses with anti-PD-1/anti-PD-L1 agents combined is 1%, whereas the reported incidence for anti-PD-L1 agents alone ranges from 1.3-5%, raising concerns for a higher overall risk. In addition to our case, only one other case reported successful resumption of immunotherapy. Early control and management of immunotherapy-induced BP may reduce complications and prevent treatment discontinuation.

Checkpoint inhibitor immunotherapy, including ipilimumab and nivolumab, is associated with numerous immune-related adverse events including dermatitis, pruritus, hepatitis, diarrhea, and hypophysitis. As the number of patients undergoing immunotherapy treatment increases, however, rare and unusual immune-related adverse events are observed. Many of these resemble known autoimmune phenomenon, such as subacute lupus erythematosus and myositis. Herein, we report a patient with metastatic serous ovarian carcinoma undergoing treatment with combination ipilimumab and nivolumab who developed subacute cutaneous lupus erythematosus (SCLE). Recent case reports have documented SCLE as a novel immune-related adverse event. In our case, she was able to successfully restart immunotherapy after a course of oral corticosteroids and maintenance oral hydroxychloroquine and topical corticosteroid therapy.

142 Background: Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties. Methods: An electronic survey was distributed to HCPs (resident physicians, attending physicians, and nurse practitioners) in the departments of dermatology, oncology, and general internal medicine (GIM) within one Midwestern hospital system. Results: Of the 62 participants (response rate: 13%), there were 19 from dermatology, 20 from oncology, and 23 from GIM. Responses were analyzed with descriptive statistics, and chi-square and ANOVA tests. There was a significant difference in the number of subjects that had heard of PCIA prior to starting the survey (Derm: 79%, Onc: 30%, GIM: 22%, p6 months) than GIM (42% and 45% vs. 17%) and significantly more had encountered patients with the condition (47% and 45% vs. 17%). More providers in dermatology and GIM knew how to diagnose PCIA compared to oncology (84% and 83% vs. 70%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA. Most providers across the three specialties believed that patients would accept PCIA treatment that was topical, oral, injectable, and required frequent administration or monitoring, but not treatment that was expensive or high risk. A majority of HCPs surveyed (94%) agreed that the diagnosis of PCIA is important. However, there was a significant difference in the confidence of HCPs in diagnosing and managing PCIA. A minority of dermatology providers (2/19) specified that they would refer to an alopecia or oncodermatology specialist, while the majority of oncology and GIM providers would refer to dermatology. Conclusions: The results of this survey identify knowledge gaps about PCIA amongst health care providers. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA as part of survivorship care.

Purpose – This paper aims to describe a new methodology for controlling highly flexible automated manufacturing cells for use in aerospace manufacturing and repair. Design/methodology/approach – The design methodology and rational of the FLEXA control architecture are described along with it implementation and testing. Findings – The trials completed so far show that the level of flexibility required can be achieved both at factory, or enterprise level, and at shop floor level. Practical implications – This work has significant practical implications through its direct applicability for aerospace and other automated manufacturing processes. Originality/value – The originality of the paper lies in the truly flexible nature of the control system described and its ability to mimic traditional cell control architectures but be expanded through the use of virtual Programmable Logic Controller to control any number of cells without the need for significant extra hardware.

Bis zum heutigen Zeitpunkt existieren fur das Transitionalzellkarzinom der Harnblase (TCC) keine Marker. Fibronektin (FN) spielt eine Rolle im Bereich der Progression und Invasion von Malignomen. Ziel dieser Studie war es, nach ersten viel versprechenden Untersuchungen die Wertigkeit von zellularem FN (cFN), eine spezifischere Subform des produzierten FN, in verschiedenen TCC-Stadien zu evaluieren.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

There is a growing market for elderly care and assisted living. This trend is followed by a need for experts and professionals in health care and assistive technology. To target this need, the University of Rostock established a further education program for Ambient Assisted Living. The program consists of three courses and addresses the topics: ‘information and communication technologies’, ‘ethics and law’, ‘consulting and communication’ as well as ‘assistive technology’ in electronic health care. The courses are student-centered and especially designed for heterogeneous groups. The participants also get the opportunity to test currently available assisted living and e-health products.

Modifications of the Child-Pugh classification of liver cirrhosis by incorporation of hyaluronan were tested to improve the prognostic power for long term evaluation of liver cirrhosis in 126 patients observed over a period of 10 years.Serum concentrations of HA were determined at study entry. Statistical analysis included Kaplan-Meier life tables and stepwise multivariant Cox-regression analysis for each parameter of Child-Pugh classification and hyaluronan. Prognostic models were developed by exchanging prothrombin time, albumin and encephalopathy by HA in different combinations.Based on a good single correlation between hyaluronan (0.62) and clinical course (P0.01) we conclude that models with hyaluronan instead of albumin or encephalopathy and with or without shifted threshold values of bilirubin and albumin are superior for the prediction of the long term prognosis. In Cox-regression analysis, apart from hyaluronan and bilirubin, no other parameters contributed to an improvement.We conclude that a modification of the Child-Pugh classification of liver cirrhosis by inclusion of HA significantly improves the predictive power of CP, especially in alcoholic etiology. A prospective validation of the newly defined scores needs to be done in the future.

Antibiotic therapy improves the outcome of severe sepsis and septic shock, however pharmacokinetic properties are altered in this scenario. Amikacin (AMK) is an option to treat community or nosocomial infections, although standard doses might be insufficient in critically ill patients. The aim of this study was to evaluate two AMK dosage regimens in comparison with standard therapy with regard to efficacy in achieving adequate plasma levels as well as safety. In total, 99 patients with severe sepsis or septic shock were randomised to different AMK dose protocols: Group 1, 25 mg/kg/day; Group 2, 30 mg/kg/day; and Group 3, historical standard dose (15 mg/kg/day). Peak plasma concentrations at 1 h (C(max)) were determined. Pharmacokinetics was determined and renal function was monitored to evaluate toxicity. Groups were compared using bilateral T-test. Demographic characteristics of the three groups were comparable. AMK C(max) values were 57.4±9.8, 72.1±18.4 and 35.2±9.4 μg/mL, respectively (P0.001 between Groups 1 and 2 versus Group 3, and P0.01 between Group 1 versus Group 2). A C(max)60 μg/mL was reached by 39%, 76% and 0% of patients in Groups 1, 2 and 3, respectively (P0.001) and creatinine clearance at Day 28 was 95.6±47.4, 89.7±26.6 and 56.4±18.4 mL/min, respectively. In conclusion, a 30 mg/kg daily dose of AMK presents significantly higher C(max) compared with the other groups, with 76% of patients reaching recommended peak plasma levels with no association with higher nephrotoxicity. Standard doses are insufficient in critically ill patients to reach the recommended C(max).

Objectives INCA (Intelligent Control Assistant for Diabetes) is an EU funded project aimed at improving diabetes therapy by creating a personal closed-loop system interacting with telemedical remote control. This study aims at identifying and applying suitable methods for a cost–benefit analysis from the perspective of the payor for health services. Methods For cost analysis MOSAIK-M was used, a method and tool for health information systems analysis and design. Two MOSAIK-M models were created describing conventional insulin pump based diabetes care (CSII), and INCA based diabetes care. Both models were parameterised with costs and simulated to determine yearly costs of diabetes management and treatment for a patient with no diabetes related complications. Probability of developing complications and their duration were determined based on the Archimedes model. It was parameterised with results of a clinical study concerning HbA1c-value changes using the INCA system compared with conventional CSII. The simulation results in form of years of disease within a 30-year time frame were multiplied with corresponding treatment costs. Results Yearly costs of conventional insulin CSII for a diabetes type 1 patient are €5908 (German health care system). Using INCA based on the clinical study setting would raise yearly costs by €2233. 24% of the INCA costs are generated by the continuous blood glucose measurement device, 5% by IT devices and services. Considering also diabetes related complications in a 30-year time frame and HbA1c value reductions from 7.9 and 7.6% (conventional CSII) to 7.5 and 7.3% (INCA) reduces the additional costs of INCA to €2102 and €2162. Conclusions The approach produces an estimation of a lower bound for cost savings concerning the treatment of diabetes related complications in a 30-year time frame. These savings alone do not prove cost efficiency of the INCA approach. Further work is needed to improve the approximation and to include indirect and intangible costs.

Introduction: The dimeric form of pyruvate kinase type M2 is overexpressed in tumor cells (TuM2-PK). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (TCC) and prostate cancer (PCA) by using a commercially available enzyme-linked immunosorbent assay for detection of TuM2-PK in plasma. Material and Methods: The TuM2-PK concentration in EDTA plasma was determined quantitatively and immunologically using an ELISA (ScheBo®Tech, Germany). We measured the TuM2-PK plasma levels of 83 patients with RCC, 30 patients with TCC and 30 patients with PCA before any therapy. 100 patients with various non-malignant urological disorders were recruited as the control group. Results: Only patients with RCC showed significantly elevated plasma levels of TuM2-PK compared to the control group (p < 0.01). We found a sensitivity of 42.6% and a specificity of 80.4% using a cut-off value of 15 U/ml (manufacturer’s recommendation). During follow-up, only 50% showed increasing plasma levels of TuM2-PK in case of metastases. Significant differences could not be detected in either TCC or PCA. Conclusions: Our data suggest that TuM2-PK is not a useful marker for TCC and PCA. Due to low sensitivity and specificity, TuM2-PK is not suitable for the diagnosis of RCC. Whether TuM2-PK may be useful in advanced RCC to control success of palliative treatment regimens is still unclear.

Data related to a certain natural area, e.g. the Mediterranean Sea, the Alps or the Danube river, is often collected at different sites in different countries. Taking the availability of public computer networks like the Internet into account, it comes to no surprise that public authorities, scientists, and the general public would like to access such data that is managed at different sites transparently and homogeneously. The creation of an appropriate information technology infrastructure raises several conceptual and technological questions, e.g., responsibilities of data collection and quality assurance, searching of inhomogeneous databases in a multilingual environment and technologies for distributed, heterogeneous, scalable information systems.

In experiments on anaesthetized dogs the arterial blood pressure and the left ventricular pressure were enhanced by intraarterial blood transfusion. The circumflex branch of the left coronary artery was perfused by constant blood pressure at 65, 100 or 200 mm Hg. After elimination of the sinus node the heart rate was kept constant at 150 beats per minute by electrical stimulation of the right auricle. The metabolically regulated component of coronary resistance of the circumflex branch was kept constant by a maximal pharmacological dilatation. On this condition the coronary blood flow decreases with increasing left intraventricular systolic pressure. The coronary resistance increases. The increasing coronary resistance with increasing intraventricular blood pressure is caused by an enhancement of the extravascular component because the perfusion pressure and hematocrit were constant, and the coronary vessel maximal dilated. The rise of coronary resistance with increasing intraventricular blood pressure depends on the height of perfusion pressure. Low perfusion pressure is combined with a marked increase, while the increase is small in the experiments with high perfusion pressure. The pathophysiological significance of the results has been discussed.

The effect of heart rate, left intraventricular end-diastolic pressure and maximal rate of left intraventricular pressure rise on the extra-vascular resistance to coronary blood flow was evaluated in 19 anesthetized dogs during maximal dilatation of the coronary arteries. The heart was externally stimulated after elimination of the sinus node. It was found that extravascular support increases with increases in heart rate, end-diastolic pressure and maximal rate of rise of left intraventricular pressure.

(1964). The In-Plant Nurse. Archives of Environmental Health: An International Journal: Vol. 9, No. 2, pp. 247-251.

In Experimenten an narkotisierten Hunden wurde durch i.v. Injektionen eines Barbiturates bei gleichzeitigen Bluttransfusionen, die den arteriellen Blutdruck konstant hielten, der enddiastolische Druck im linken Ventrikel erhoht. Die Herzen wurden nach Ausschalten des Sinusknotens uber das rechte Herzohr elektrisch mit 150 Impulsen in der Minute stimuliert. Die metabolische Komponente des Einfluswiderstandes wurde durch eine pharmakologische, maximale Dilatation der Coronargefase konstant gehalten. Die Coronardurchblutung bei maximaler pharmakologischer Dilatation sinkt mit steigendem end-diastolischen Druck ab. Die extravasale Komponente des Einfluswiderstandes steigt mit zunehmendem enddiastolischen Druck wahrend der Systole, der Diastole und des Gesamtcyclus an. Die Systolendauer nimmt mit steigendem enddiastolischen Druck zu.

Quality of software in Man-machine systems was often defined. For the acceptance of MMS by the users criterions understandability and learnability are essential. These criterions will be fullfilled best, if the learnability of the users is regarded in the software. That will be reached, if side by side components for prefered use during learning and components for prefered use by experienced users in permanent running are included in the software. And this will be reached best by the principle “software development with and by the users“.

Quality of software in Man-machine systems was often defined. For the acceptance of MMS by the users criterions understandability and learnability are essential. These criterions will be fullfilled best, if the learnability of the users is regarded in the software. That will be reached, if side by side components for prefered use during learning and components for prefered use by experienced users in permanent running are included in the software. And this will be reached best by the principle “software development with and by the users”.

The influence of increasing perfusion pressure in the coronary arteries on cardiac contractility and oxygen consumption was studied in isovolumetrically working, empty beating, and potassium arrested guinea-pig hearts. Raising the coronary perfusion pressure from 60 to 80 cm H2O increased left ventricular peak systolic pressure by 19.4±2.8%, coronary flow by 47.7±8.0% and oxygen consumption by 32.7±6.2% (N=17). At a constant perfusion pressure hypoxia increased the coronary flow by 111.8±16.4% (N=19), but did not alter the contractility of the heart or its oxygen consumption. Increasing pressure without changing flow, raised pressure in the left ventricle by 26.5±4.8% and myocardial oxygen consumption by 20.3±3.4% (N=14). The end-diastolic pressure and the heart rate remained unchanged in all experiments. From these findings it may be concluded that the pressure in the coronary vessels — independent of the flow rate — exercises a positive inotropic effect, thereby increasing metabolism. This can be explained by increased fibre tension, caused by an extension of the coronary vessels, the so-called “garden-hose-effect”.