Let us talk about death: gender effects in cancer patients' preferences for end-of-life discussions.

PURPOSE: Patients with advanced cancer often receive suboptimal end-of-life (EOL) care. Particularly males with advanced cancer are more likely to receive EOL care that is more aggressive, even if death is imminent. Critical factors determining EOL care are EOL conversations or advance care planning. However, information about gender-related factors influencing EOL conversations is lacking. Therefore, the current study investigates gender differences concerning the content, the desired time point, and the mode of initiation of EOL conversations in cancer patients. METHODS: In a cross-sectional study, 186 female and male cancer patients were asked about their preferences for EOL discussions using a semi-structured interview, focusing on (a) the importance of six different topics (medical and nursing care, organizational, emotional, social, and spiritual/religious aspects), (b) the desired time point, and (c) the mode of discussion initiation. RESULTS: The importance of EOL topics differs significantly regarding issue (p = 0.002, η2 = 0.02) and gender (p < 0.001, η2 = 0.11). Males wish to avoid the engagement in discussions about death and dying particularly if they are anxious about their end-of-life period. They wish to be addressed regarding the "hard facts" nursing and medical care only. In contrast, females prefer to speak more about "soft facts" and to be addressed about each EOL topic. Independent of gender, the majority of patients prefer to talk rather late: when the disease is getting worse (58%), at the end of their therapy, or when loosing self-sufficiency (27.5%). CONCLUSION: The tendency of patients to talk late about EOL issues increases the risk of delayed or missed EOL conversations, which may be due to a knowledge gap regarding the possibility of disease-associated incapability. Furthermore, there are significant gender differences influencing the access to EOL conversations. Therefore, for daily clinical routine, we suggest an early two-step, gender-sensitive approach to end-of-life conversations.

Breaking bad news-what patients want and what they get: evaluating the SPIKES protocol in Germany.

BACKGROUND: Evaluation of the SPIKES protocol, a recommended guideline for breaking bad news, is sparse, and information about patients' preferences for bad-news delivery in Germany is lacking. Being the first actual-theoretical comparison of a 'breaking bad news' guideline, the present study evaluates the recommended steps of the SPIKES protocol. Moreover, emotional consequences and quality of bad-news delivery are investigated. PATIENTS AND METHODS: A total of 350 cancer patients answered the MABBAN (Marburg Breaking Bad News Scale), a questionnaire representing the six SPIKES subscales, asking for the procedure, perception and satisfaction of the first cancer disclosure and patient's assign to these items. RESULTS: Only 46.2% of the asked cancer patients are completely satisfied with how bad news had been broken to them. The overall quality is significantly related to the emotional state after receiving bad news (r = -0.261, P < 0.001). Patients' preferences differ highly significantly from the way bad news were delivered, and the resulting rang list of patients' preferences indicates that the SPIKES protocol do not fully meet the priorities of cancer patients in Germany. CONCLUSIONS: It could be postulated that the low satisfaction of patients observed in this study reflects the highly significant difference between patients' preferences and bad-news delivery. Therefore, some adjunctions to the SPIKES protocol should be considered, including a frequent reassurance of listeners' understanding, the perpetual possibility to ask question, respect for prearrangement needs and the conception of bad-news delivery in a two-step procedure.

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages.

All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 µg · kg(-1) body weight) versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1ß, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-α, nuclear factor-κB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma.

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.

TNF-alpha-, TNF-beta-, IL-6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. In the present case-control study, we investigated interleukin (IL)-promoter polymorphisms known to correlate with altered transcription levels of their gene products in patients with COPD. We analyzed tumor necrosis factor-alpha (TNF-alpha)-308, TNF-beta-intron1-252, IL-6-174, IL-10-819, and IL-10-1082 polymorphisms in 469 individuals using restriction fragment length polymorphism-based converted polymerase chain reaction. The study population consisted of 113 patients with COPD based on chronic bronchitis, divided into subgroups by severity (I degrees -III degrees ), 113 matched hospitalized individuals suffering from severe coronary heart disease without pulmonary disease (age-, sex-, and smoking-matched control group), and 243 healthy individuals (population control group). The matched analysis showed no significant differences in genotype distribution of all tested polymorphisms between the matched controls and the COPD patients. However, comparison with the population controls revealed significant differences in IL-10-1082 A/G genotype frequencies (P = 0.0247 for the whole COPD group, P = 0.009 for smokers only), with the genotypes carrying the G allele more common in the COPD cases [odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.01-2.75; P = 0.046]. Interestingly, this shift toward more G alleles was even more pronounced in the matched control group (OR = 2.55, 95% CI 1.47-4.41; P = 0.0007), suggesting both presented groups share corresponding underlying mechanisms. The IL-10-1082_G allele is known to correlate with altered IL-10 levels. Therefore, it might be associated with altered or abnormal inflammatory response, a mechanism that could be postulated to be important in both chronic bronchitis and coronary heart disease.

[64-year old woman patient with severe pain and alterations of sensibility]. / 64-jährige Patientin mit starken Schmerzzuständen und Sensibilitätsstörungen.

The differential diagnosis of chronic pain is not seldom difficult, particularly if additional symptoms or laboratory tests are not specific, and small but important signs are not correctly analyzed and overlooked. We present a case of sarcoidosis with central involvement showing these diagnostic problems.

Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients.

Genetic factors are thought to influence the risk for lung cancer. Since pulmonary surfactant mediates the response to inhaled carcinogenic substances, candidate genes may be among those coding for pulmonary surfactant proteins. In the present matched case-control study a polymorphism within intron 4 of the gene coding for surfactant specific protein B was analysed in 357 individuals. They were divided into 117 patients with lung cancer (40 patients with small cell lung cancer, 77 patients with non small cell lung cancer), matched controls and 123 healthy individuals. Surfactant protein B gene variants were analysed using specific PCR and cloned surfactant protein B sequences as controls. The frequency of the intron 4 variation was similar in both control groups (13.0% and 9.4%), whereas it was increased in the small cell lung cancer group (17.5%) and the non small cell lung cancer group (16.9%). The gene variation was found significantly more frequently in patients with squamous cell carcinoma (25.0%, P=0.016, odds ratio=3.2, 95%CI=1.24-8.28) than in the controls. These results indicate an association of the surfactant protein B intron 4 variants and/or its flanking loci with mechanisms that may enhance lung cancer susceptibility, especially to squamous cell carcinoma of the lung.

[Paraparesis and sensory spinal cord transection caused by an NK-cell lymphoma]. / Paraparese und sensibler Querschnitt bei NK-Zell-Lymphom.

HISTORY AND ADMISSION FINDINGS: A 42-year-old man of Russian origin was admitted because of fever, nocturnal sweating and weight loss. Within 2 days a paraparesis of the legs and a bladder-colon disorder had developed. Neurological examination suggested a spinal cord lesion at T4 and hypaesthesia from T9 downward. INVESTIGATIONS: Lymphocytosis was associated with an increase in NK-cells (63% NK-cells; CD16 positive, CD56 negative). Chromosomal findings were: (46 XY ad (1) (P372), ad (3) (P25), DEL (14) Q22 (Q24), RG (5) (RG). Electrophysiological tests indicated a symmetrical prolonged central motor conduction time. Magnetic resonance imaging showed opacification of all nasal sinuses. Histological findings of a biopsy from this site were suspicious of NK-cell lymphoma. DIAGNOSIS, TREATMENT AND COURSE: The neurological symptoms briefly responded to glucocorticoids, but were resistant to chemotherapy. Plasmapheresis, undertaken on the tentative diagnosis of paraneoplastic protein secretion, brought definite improvement in the overall condition. A highly malignant lymphoma was diagnosed 12 months later. It, too, proved to be treatment-refractory. CONCLUSION: A cerebrospinal tap should be routinely performed in patients with NK-cell lymphoma. In view of the poor prognosis, early escalation of treatment should be considered.

Effect of N-acetylcysteine treatment on NO2-impaired type II pneumocyte surfactant metabolism.

Inhalation of nitrogen dioxide (NO2) is known to alter the composition of the bronchoalveolar lavage (BAL) and to impair the surfactant metabolism of type II pneumocytes. However, information is sparse as to whether application of the widely used antioxidant N-acetylcysteine (NAC) is capable of preventing or reducing these alterations. The aim of the study was to investigate if in vivo administration of NAC to NO2-inhaling rats protected BAL parameters and physiology of type II pneumocytes from impairment. For this purpose, rats were exposed to 720 p.p.m. h-1 NO2, that was applied continuously, intermittently or repeatedly. During inhalation one group of rats received saline and the other group received NAC antioxidant (200 mg kg-1, intraperitoneally) once a day. The BAL protein and phospholipid content increased most in the continuously and repeatedly NO2-exposed rats when compared to the controls, while the intermittent exposure did not change these parameters. Application of NAC led to a marked decrease of the protein elevation for the continuously and intermittently exposed groups, but exhibited no influence on the BAL phospholipid. Surprisingly, all NO2 exposure modes elevated the glutathione content (reduced and oxidized) in the BAL. Application of NAC clearly decreased the content of both forms of glutathione in the continuously and the repeatedly NO2-exposed groups. Phospholipid synthesis, measured by choline uptake into type II cells, was increased most after continuous NO2 inhalation. The NAC reduced this increase moderately. Whereas choline uptake by type II cells was obviously stimulated by NO2, the stimulated secretion of phosphatidylcholine from these cells was decreased by this oxidant. Only continuous exposure reduced this activity markedly. The NAC clearly restored the impaired secretion activity in the cells from the continuously NO2-exposed animals. Since the efficacy of NAC in the prevention of NO2-induced impairments in the surfactant system is striking mainly in the continuously exposed group, we suggest that administration of NAC to NO2-induced lung injury partially restores altered BAL components and the impaired physiology of type II pneumocytes.

alpha-tocopherol improves impaired physiology of rat type II pneumocytes isolated from experimentally injured lungs.

BACKGROUND: Oxidant stress delivered by nitrogen dioxide (NO2) inhalation impairs the function of extracellular surfactant as well as surfactant phospholipid metabolism in type II pneumocytes. Because protection against oxidant stress is important to normal lung function, the lung contains a variety of antioxidants, including vitamin E. Whether administration of this antioxidant during NO2 inhalation attenuates NO2-induced alterations in phospholipid metabolism in type II pneumocytes has not been studied. METHODS: We exposed rats to identical NO2 body doses (720 p.p.m. x h) using continuous, intermittent, or repetitive protocols. During exposure periods, the animals received daily intramuscular injections of vitamin E (25 mg kg-1). We isolated type II pneumocytes from NO2-exposed rats and evaluated them for cell yield and viability, as well as for synthesis and secretion of phosphatidylcholine (PC) as measures of surfactant metabolism. RESULTS: The yield of type II pneumocytes was significantly elevated from animals that had been exposed continuously to NO2 whereas in intermittently and repeatedly exposed rats, cell yield was similar to yield from control animals. Viability of the isolated cells was similar in controls and all NO2 exposure protocols. Vitamin E treatment of the NO2-exposed rats neither changed cell yield nor cell viability. Phospholipid de novo synthesis, as estimated by choline incorporation into PC, was increased most after continuous NO2 inhalation whereas in the other conditions there was only a slight increase. Vitamin E administration further increased phospholipid synthesis; this difference reached statistical significance only in the case of intermittent NO2 exposure. Secretion of phosphatidylcholine from type II cells was only reduced after continuous NO2 inhalation and administration of the antioxidant reduced the impairment. CONCLUSION: Because vitamin E appears to preserve the ability of type II pneumocytes isolated from NO2-exposed rats to synthesize and secrete surfactant lipid, we conclude that administration of vitamin E may mitigate NO2-induced lung injury.

Diagnostic and therapeutic consequences of repeat brain imaging and follow-up vascular imaging in stroke patients.

BACKGROUND AND PURPOSE: Recently, the diagnostic and therapeutic importance of repeat radiologic imaging in stroke patients has been questioned. The aim of this study was to show the therapeutic and diagnostic consequences of both repeat brain imaging and follow-up vascular imaging in this group of patients. METHODS: Neuroradiologic images and reports as well as clinical records of 317 patients (209 men and 108 women; mean age, 63 years) were reviewed retrospectively to determine the number of modifications made to the diagnosis and therapeutic regimen and to the classification of neuroradiologic findings. RESULTS: Two hundred thirty-eight repeat imaging procedures were performed in 171 patients. Of these, 76 were vascular imaging examinations (11 CT angiograms, 13 MR angiograms, 52 digital subtraction angiograms) and 162 were cross-sectional brain imaging studies (54 MR images, 108 CT scans). Forty of the 76 vascular imaging procedures and 77 of the 162 repeat cross-sectional brain imaging studies led to important diagnostic modifications with consequences for the patients' therapy and prognosis. CONCLUSION: Our study establishes that vascular imaging methods as well as cross-sectional brain imaging used as repeat imaging procedures in stroke patients can have important diagnostic and therapeutic consequences. We believe that repeat imaging in selected subgroups will be cost-effective.

Effect of air pollutants on the pulmonary surfactant system.

Air pollutants have been recognized to influence the structure and function of the surfactant system. Agents that have received the most attention include ozone, nitrogen dioxide, hyperoxia, diesel exhaust, tobacco smoke, silica and fibrous materials such as asbestos. The deleterious effects of air pollutants on the surfactant system depend on the size of the agent, on its solubility in aqueous solutions and chemical reactivity and on its concentration and the duration of exposure. Hereby the following general rules apply: the smaller the agent's size and the less water soluble the pollutant is, the greater the tendency to reach the alveoli during breathing. In addition, the reactivity also determines the depth of penetration into alveoli. Compounds with high reactivity such as O3, which also fulfil the earlier rules, will react with the upper respiratory tract compared with compounds with slightly reduced reactivity, such as NO2, which will penetrate the alveoli. The common consequence of exposure to air pollutants is an accumulation of surfactant phospholipids and surfactant-specific proteins in the bronchoalveolar lavage fluid. These components also are structurally altered, mainly by oxidant gases, resulting in impairment of their biological activity. Thus, for surfactant phospholipids, there is impaired adsorption to the air-liquid interface due to oxidation of their fatty acids. Also, surfactant protein A, regarded as a modulator of the surfactant system, shows impaired functions after exposure to oxidants. It is likely that in addition to the effects described in this review not all effects are known because the molecular effects of several key components (e.g. SP-B and C) have not been well studied.

Adaptation of rat type II pneumocytes to NO2: effects of NO2 application mode on phosphatidylcholine metabolism.

Previous studies have shown that nitrogen dioxide (NO2) inhalation affects the extracellular surfactant as well as the structure and function of type II pneumocytes. Since in these studies there were great variabilities in oxidant concentration, duration of exposure, and mode of NO2 application, we evaluated the influence of the NO2 application mode on the phospholipid metabolism of type II pneumocytes. Rats were exposed to identical NO2 body doses (720 ppm x h), which were applied continuously (10 ppm for 3 d), intermittently (10 ppm for 8 h per day, for 9 d), and repeatedly (10 ppm for 3 d, 28 d rest, and then 10 ppm for 3 d). Immediately after exposure, type II cells were isolated and evaluated for cell yield, vitality, phosphatidylcholine (PC) synthesis, and secretion. Type II pneumocyte cell yield from animals that had been continuously exposed to NO2 was significantly increased, whereas intermittently and repeatedly treated rats exhibited cell yields that were nonsignificantly enhanced. Vitality of the isolated type II pneumocytes was not affected by the NO2 exposure modes. Continuous application of 720 ppm x h NO2 resulted in increased activity of the cytidine-5-diphosphate (CDP)-choline pathway. After continuous NO2 application, specific activity of choline kinase, cytidine triphosphate (CTP):cholinephosphate cytidylyltransferase, uptake of choline, and pool sizes of CDP-choline and PC were significantly increased over those of controls. Intermittent application of this NO2 body dose also provoked an increase in PC synthesis, but this increase was less prominent than after continuous exposure. After repeated exposure, the synthesis parameters were comparable to those for cells from control animals. Whereas PC synthesis in type II cells was obviously stimulated by NO2, the secretory activity of the cells was reduced. Continuous exposure reduced this activity most, whereas intermittent exposure nonsignificantly reduced this activity as compared with that of controls. The repeated application of NO2 produced no differences. We conclude that type II pneumocytes adapt to NO2 atmospheres depending on the mode of its application, at least for the metabolism of PC and its secretion from isolated type II pneumocytes. Further studies are necessary to determine whether additional metabolic activities will also adapt to NO2 atmospheres, and if these observations are specific for NO2 or represent effects generally due to oxidants.

[Echocardiography quantification of mitral valve defects]. / Echokardiographische Quantifizierung von Mitralklappenfehlern.

Echocardiography led during the last 10 years to a definite improvement of quality of cardiological diagnostics. In addition to an excellent recording of morphological and functional changes of the heart by 1- and two-dimensional images Doppler-echocardiography allows the semiquantitative judgement of the hemodynamic effect. Echocardiographic techniques try to measure the mitral valve area in cases of mitral stenosis resp. the leak area in cases of mitral insufficiency to assess the importance of valve disorder. These parameters are constant values, whereas the transmitral diastolic pressure gradient and the regurgitant volume are variable. The assessment of the mitral valve area and the graduation of the mitral valve stenosis is possible with a high diagnostic relevance using planimetrical and/or pressure-half-time methods. The applicability of the pressure-half-time method depends on the nature of the pressure decrease and an individual review is necessary. The measurement of the leak area is much more problematical. The assessment of the functional regurgitation area by colour coded Doppler-echocardiography seems to be favourite, but not validated up to now. A semiquantitative judgement of a mitral valve insufficiency is successful in evaluating of intensity, width and area of the regurgitant cloud. The evaluation of raw data of flow patterns will provide further information in future.

[Pre- and postoperative computer tomography diagnosis of aortic isthmus stenosis]. / Prä- und postoperative computertomographische Diagnostik der Aortenisthmusstenose.

In individual cases the computed tomography renders possible the ascertainment of the coarctation of the aorta. Despite modified examination method (secondary section technique, continuous application of contrast medium) the reliability is insignificant. Therefore, the method cannot be recommended for the primary diagnostics of the coarctation of the aorta. The computed tomography is extraordinarily suited for the detection of aneurysms of anastomoses after operation of coarctations of the aorta. In 50 computed-tomographic examinations of 48 patients 11 times an aneurysm could be ascertained. This high proportion of late postoperative complications is above all to be traced back to the surgical suture material used in the sixties. There were only two falsely positive findings, in which cases also here relevant pathological changes were present. The computed tomography can more exactly than the aortography adopt a definite attitude to the question of the dissection of prostheses or to pseudoaneurysms.

[12 years' analysis of serum fatty acids--final results of the Leipzig Longitudinal Gerontologic Study]. / 12-Jahres-Analyse von Serumfettsäuren--abschliessende Resultate der Leipziger Gerontologischen Longitudinalstudie.

In the Leipzig longitudinal study performed from 1968 to 1980 in 383 test persons with healthy metabolism in 2-3 years time intervals gas-chromatographic analyses of the serum fatty acid pattern were carried out. In dependence upon age, sex, and body-weight the vasoprotective linoleic, linolenic and arachidonic acid increased and the vasoaggressive palmitic and eicosatrienic acid decreased. Influences of age as well as the change of the feeding habits are causally discussed for this purpose.

[Long-term behavior of serum fatty acids--results of a Leipzig gerontologic longitudinal study]. / Untersuchungen zum Langzeitverhalten von Serumfettsäuren--Ergebnisse der Leipziger gerontologischen Longitudinalstudie.

In the Leipzig longitudinal study performed from 1968 to 1980 in 383 test persons with healthy metabolism in 2-3--year time intervals gas-chromatographic analyses of the serum fatty acid pattern were carried out. The dependence upon age, sex, and body-weight the vasoprotective linoleic, linolenic and arachidonic acid increased and the vasoaggressive palmitinic and eicosatrienic acid decreased. Influences of age as well as the change of the feeding habits are causally discussed for this purpose.

Selected metabolic results of the Leipzig gerontological longitudinal study.

The results of the longitudinal study show a gradual development of the overweight of young obese women. The decrease of weight in middle aged obese women is likely to be influenced by additional therapeutic measures by the physicians. It is interesting to note that men and women of normal weight do not develop overweight over a ten-years-span. Serum cholesterol increased in all age and weight groups within a ten-years-interval. The changes of the shares of total fatty acids were especially characterized by the decrease of palmitic acid and the increase of linoleic acid in the ten-years-interval. However age, weight and sex differences were present. The increase of uric acid level occurred with all test persons independent of sex. With test persons above 45 years a significant sex difference was noticed.

[Behavior of serum lipid parameters--results of a longitudinal gerontologic study]. / Verhalten von Serumlipidparametern-Ergebnisse einer gerontologischen Longitudinalstudie.

Within the Leipzig longitudinal study from 1968 to 1978 in 158 test persons (46 males, 112 females) cholesterol and the total fatty acid spectre were gas-chromatographically determined in regular intervals. Serum cholesterol as well as proportions of linoleic acid increased significantly. By the significant decrease of the palmitic acid the percentages of the saturated fatty acids altogether decreased despite increase of stearic acid. In these cases the differences between males and females as well as between persons with normal weight and overweight more and more evened up. Ascertained correlations existed between reduction of the relative weight and decrease or more insignificant increase of cholesterol on the one hand and increase of linoleic acid on the other. The latter phenomenon is above all to be traced back to the fat-reduced diet and to the diet rich in polyene fatty acids which was more and more applied mainly by older test persons in the course of the longitudinal study, which thus may lead to antiatherogenic constellations of serum fatty acids.