Can a stressed oncologist be good in a consultation? A qualitative study on the oncologists' perception.

The aim of this exploratory study was to examine how the working conditions and job stress of private practice oncologists (PPOs) affect their interaction with patients. Data for the study were collected through semi-structured interviews with PPOs selected based on purposeful sampling criteria. The data were evaluated using content analysis. Factors perceived by PPOs to influence their level of stress and patient care were some of their own personal characteristics as well as working conditions both within and outside their practices. Apart from being able to name specific stressors (e.g., dysfunctional organisational workflow and interruptions during medical encounters), the oncologists also mentioned individual and organisational resources (e.g., professional experience, well-educated nurses and good work organisation) for coping with job stress and improving interaction with patients. Within this study, we identified some obstacles on the individual and organisational level for good patient care, as working conditions which might lead to time pressure and stress, which subsequently have an impact on quality in patient care (e.g., less time for personal issues during patient consultations). Future stress research should conduct a more in-depth investigation of these and other interventions at both the individual and organisational levels in order to improve patient care.

[A rare cause of hepatic coma]. / Seltene Ursache eines hepatisch bedingten Komas.

CASE REPORT: A 65-year-old female patient was admitted to the hospital in somnolent state. During physical examination, she had an increase in blood pressure and a positive bilateral Babinski's sign. Laboratory findings showed elevated liver enzymes, metabolic alkalosis and slightly elevated kidney values. 3 h hours later she lapsed into a hepatic coma (ammonia > 400 micrograms/dl). Subsequently, indirect anamnesis revealed the following affections: ureterosigmoidostomy in 1942, cystectomy in 1943, and right-sided nephrectomy in 1950. DISCUSSION: This case presents with an uncommon origin of the hepatic encephalopathy: in the operated colon, bacterial overgrowth (bacteriogenic ureapoiesis) developed, which led to a hyperammonemia. Furthermore, in mild alcoholic liver disease--as in this case--ammonia cannot be metabolized to urea and leads to hepatic encephalopathy. We considered making this part of the colon poor in bacteria (by consequent administration of antibiotics), thus reducing the formation of ammonia.

Elevated cell-associated levels of interleukin 1beta and interleukin 6 in inflamed mucosa of inflammatory bowel disease.

The aim of this study was to investigate the involvement of the monocyte-derived cytokines interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in idiopathic inflammatory bowel disease. Endoscopic biopsies of normal and inflamed intestinal mucosa were obtained from patients with ulcerative colitis (n = 11) and with Crohn's disease (n = 10). Intestinal mucosal cells were isolated by collagenase digestion. Cell viability, morphology and CD14 expression were determined. To measure cell-associated cytokine levels, cells were lysed and analysed for IL-1beta and TNF-alpha in specific radioimmunoassays and for IL-6 using a biological assay. Compared with mucosal cells from control patients without inflammatory bowel disease the inflamed intestine in ulcerative colitis and Crohn's disease displayed markedly enhanced levels of IL-1beta (median 245 pg 10(-6) cells, range 30-1275) and IL-6 (median 22 U 10(-6) cells, range 1-298). Non-inflamed mucosa in patients with ulcerative colitis and Crohn's disease did not show elevated levels of IL-1beta (median 50 pg 10(-6) cells, range 33-90) or IL-6 (mean below detection limit of assay, i.e. 1 U 10(-6) cells). In contrast, no clear cut difference between inflamed and non-inflamed mucosa could be detected for TNF-alpha. High tissue levels of IL-6 were associated with a high endoscopic grade of local inflammation. These results suggest that the monocyte-derived cytokines IL-1beta and IL-6 are mediators of inflammation in inflammatory bowel disease.

Calibration of misonidazole labeling by simultaneous measurement of oxygen tension and labeling density in multicellular spheroids.

To correlate misonidazole concentrations and oxygen pressures (Po2) at identical locations within EMT6/Ro multi-cell spheroids (mean diameters +/- SD: 867 +/- 20 microns), Po2 measurements were performed with oxygen-sensitive microelectrodes during incubation of these spheroids with tritiated misonidazole (10 mg/I; 445 microCi/mg). In each individual spheroid, Po2 profiles were correlated with the corresponding spatial distribution of misonidazole as quantified by conventional autoradiography and grain counting. To compare the oxygenation status of spheroids in the measuring chamber with that of spheroids in spinner culture, misonidazole labeling was performed in both environments following the same protocol. All experiments were conducted in 20% oxygen and BME or in 5% oxygen and DMEM to obtain spheroids with different degrees of oxygenation. Labeled misonidazole was fairly evenly distributed in the outer, better oxygenated regions of EMT6 spheroids. In contrast, there was an accumulation of the labeled substance near central necrosis where low oxygen tensions were measured. Grain densities were similar at corresponding oxygen pressures under both environmental conditions. Except for some scatter, grain density as a function of oxygen pressure showed little variation in the Po2 range of 20-60 mm Hg, but exhibited a steep increase below 10 mm Hg. The findings imply that a substantial rise in local misonidazole labeling indicates a metabolically active tissue region at low Po2 that is not necessarily identical with the radiobiologically hypoxic cell fraction. A comparison of the labeling densities of spheroids in spinner flasks and in the Po2 measuring chamber indicates that oxygenation of spheroids is better in rotation culture than during microelectrode measurements.

Proliferation and oxygenation status of widr spheroids in different lactate and oxygen environments.

Human colon adenocarcinoma cells WiDr were cultured as monolayers or multicellular spheroids in 5% or 20% (v/v) oxygen and in various external lactate concentrations of 0-20 mM. Doubling times and H-3-thymidine labeling indices of exponential monolayer cells indicated that there was no difference in growth behavior between the two oxygen environments, yet these parameters reflected a growth retardation upon elevation of lactate. Growth of WiDr spheroids was retarded in both low oxygen and high lactate concentrations. There was a tendency towards a decrease in the thickness of the viable cell rim with increasing lactate in 20% O-2, whereas the width of the viable rim increased significantly as a function of external lactate in 5% O-2. Intraspheroidal oxygen tensions (Po-2) measured with microelectrodes were less in 5% O-2 than in 20% O-2, yet did not vary systematically as a function of external lactate. Po-2 values in the spheroid center dropped to 0 mm Hg prior to the emergence of central necrosis under all conditions investigated. Unlike numerous other spheroid types investigated up to now, WiDr spheroids mimic tumor microregions with hypoxia-induced necrosis and with nonproliferating cells at very low oxygen pressure.

Enteric protein loss as a marker of intestinal inflammatory activity in Crohn's disease: comparability of enteric clearance and stool concentration of alpha-1-antitrypsin?

Intestinal alpha 1-antitrypsin (alpha 1-AT) clearance has been shown a reliable index of intestinal inflammatory activity in Crohn's disease (CD). For reasons of practicability, it has been repeatedly suggested to replace alpha 1-AT clearance by alpha 1-AT concentration in random stool samples. In 60 controls and in 70 patients with CD, in 21 patients before and after treatment, fecal alpha 1-AT concentration and the ratio of stool and serum alpha 1-AT concentration were compared with alpha 1-AT clearance. In 11 patients alpha 1-AT clearance, fecal concentration and stool/serum alpha 1-AT concentration ratio were compared with 51Cr-albumin clearance. alpha 1-AT clearance (104 +/- 14 vs. 17.5 +/- 2 ml/d, p < 0.0001) as well as fecal alpha 1-AT concentration (155 +/- 21 vs. 30 +/- 3 mg/100 ml, p < 0.0001) and stool/serum alpha 1-AT concentration ratio (45 +/- 6 vs. 12 +/- 1) were significantly higher in CD patients than in controls. alpha 1-AT clearance (60 +/- 9 vs. 37 +/- 4 ml/d, p < 0.01), fecal alpha 1-AT concentration (113 +/- 21 vs. 59 +/- 8 mg/100 ml, p < 0.01) and the stool/serum alpha 1-AT concentration ratio (27 +/- 4 vs. 18 +/- 2) decreased after treatment, but fecal alpha 1-AT concentration and the stool/serum alpha 1-AT concentration ratio failed to parallel the course of alpha 1-AT clearance in 33% and in 24% of patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Proliferation-associated oxygen consumption and morphology of tumor cells in monolayer and spheroid culture.

The oxygen consumption rate, proliferative activity, and morphology of EMT6/Ro mouse mammary sarcoma cells in monolayer and multicellular spheroid culture have been investigated in a comparative study. During the transition of monolayer cells from the exponential into the plateau growth phase, there is a distinct decrease in the cellular volume that is associated with a corresponding decrease in the proliferative and respiratory activity of the cells. The decline in cell volume is mainly due to a decrease in the content of cytoplasm, whereas the size of the nucleus is only slightly reduced. A concomitant decrease in the number of mitochondria per cell obviously accounts for the reduction in cellular oxygen uptake. Despite a continuous decrease of cell proliferation from the surface to interior regions of EMT6 spheroids reflected by a gradient in tritiated thymidine labeling, volume-related oxygen consumption is rather uniform in viable regions of these aggregates. The finding can be explained by the results of the morphometric evaluation showing a uniform volume density of mitochondria, i.e., of oxygen-consuming sites within these spheroids.

Rhabdomyosarcoma spheroids with central proliferation and differentiation.

A novel type of multicellular spheroids was established and characterized with regard to growth behavior, proliferation, and differentiation. The spheroids were grown from clonal rat rhabdomyosarcoma cells using the spinner flask technique. The cell aggregates showed several unique properties that were different from those observed in most of the spheroids investigated to date. These properties include a non-Gompertzian volume growth; the coexistence of undifferentiated mononuclear cells and of differentiated, myotube-like giant cells with numerous nuclei; a relatively homogeneous intraspheroidal distribution of proliferating mononuclear cells with thymidine labeling even in the center of spheroids greater than 1 mm; the absence of necrosis in such large spheroids, and the accumulation of myotube-like cells in the center of these spheroids instead. There was a decrease in the overall proliferative activity of the mononuclear cells with increasing proportion of giant cells in the rhabdomyosarcoma spheroids.

Pathophysiological approaches to identifying tumor hypoxia in patients.

The present report summarizes observations of the authors on tumor oxygenation and on techniques for characterizing tumor hypoxia in patients. Cryospectrophotometric measurements of HbO2 saturations in tumor microvessels allow for estimates of the proportion of well oxygenated tissue regions. Labeling of tissue areas at oxygen (O2) tensions (pO2) less than 10 mm Hg with misonidazole may be used for a general characterization of the oxygenation status in patient tumors rather than for the determination of the radiobiologically hypoxic cell fraction. Quantitative bioluminescence and single photon imaging make it possible to determine ATP concentrations in absolute terms with a spatial resolution at the cellular level. It is shown that the ATP distribution reflects the efficiency of the O2 supply to tumors. Since all these techniques rely on biopsy material, the measured values can be assessed in relation to the histological structure and vascular pattern of the tumors. Such a direct interrelationship is not obtained when using polarographic microelectrodes in tumor tissue. However, a novel technology, the "computerized pO2 histography" has enabled direct polarographic measurements of pO2 values in patients, in extended and systematic clinical trials. Preliminary results in cervix and breast cancers demonstrate that pO2 values are lower in tumors than in adjacent normal tissues, and that great intra- and intertumoral differences occur even among tumors of the same clinical stages and histological grades, illustrating the necessity of such a pathophysiological approach to an "individualization" of tumor therapy.

Enteric protein loss in various gastrointestinal diseases determined by intestinal alpha 1-antitrypsin clearance.

Intestinal protein loss was measured by means of faecal alpha 1-antitrypsin clearance (alpha 1 ATC) in patients with various gastrointestinal diseases. In healthy controls and in patients with various gastrointestinal diseases there is a remarkable intraindividual fluctuation of the faecal protein loss from day to day. Alpha 1 AT clearance calculated from a three-day stool collection is usually sufficient to indicate enteric protein loss in Crohn's disease, ulcerative colitis, celiac sprue, and Whipple's disease. However, in two patients with intermittent diarrhea coinciding with edema and hypalbuminemia excessive enteric protein loss was observed on one day during a two week stool sampling period only. In one of these patients suction biopsies showed histologically intestinal lymphangiectasia of a 10 cm segment of the upper jejunum. The alpha 1 ATC is a suitable and cheap method to determine enteric protein loss without the use of radioactive tracers and therefore can be used in clinics without departments of nuclear medicine. In contrast to the conventional Gordon test the use of the endogenous marker alpha 1 AT facilitates the determination of faecal protein loss over long time periods, which might be of value in the diagnosis of intermittent occurring enteric protein loss. Furthermore, the endogenous marker alpha 1 AT is of use in following the course of illness and in monitoring the efficacy of therapy in patients with enteric protein loss.

Comparison of maximal postprandial serum cholylglycine concentration with the retention of 75Se-homotaurocholic acid in ileal dysfunction.

The retention of 75Se-homotaurocholic acid (75SeHCAT) was measured in 12 healthy controls and in 21 patients with Crohn's disease and compared with the maximum postprandial rise in the serum concentration of cholylglycine (CG) in order to detect bile acid malabsorption. The retention of 75SeHCAT was lowered in all patients with inflammation or resection of the terminal ileum over a length more than 20 cm. In 64% of these patients bile acid malabsorption could also be detected by the absence of a significant rise of the postprandial CG serum level but only if the loss of the ileal function exceeded 30 cm. Although less sensitive than the 75SeHCAT retention, the CG method is simpler to apply in terms of laboratory technology and does not involve exposure to radioactivity. The CG method appears to be of use to detect bile acid malabsorption in certain cases. In the case of negatively if still bile acid malabsorption is suspected more sensitive tests such as 75SeHCAT retention should be carried out to further evaluate bile acid malabsorption.

Interrelationship among morphology, metabolism, and proliferation of tumor cells in monolayer and spheroid culture.

The proliferative activity of tumor cells is positively correlated with the cellular respiration rate. Thus, a decrease in the proliferative fraction during monolayer growth of EMT6 cells is associated with a decrease in the oxygen consumption rate both per cell and per cellular volume. These changes are paralleled by variations in the morphology of the tumor cells. The cellular volume, the cytoplasmic volume, the number and volume of mitochondria is decreased, whereas the volume of the nucleus remains relatively constant during the transition of cells from the exponential to the plateau growth phase. Similar observations have been made in outer, highly proliferative and inner non-proliferating cells in EMT6 spheroids. However, the local oxygen consumption in this three dimensional, tissue-like assemblage of cells is obviously modified by the cellular packing density leading to a rather uniform oxygen uptake in the proliferating and non-proliferating cell areas.

Simplified determination of intestinal protein excretion based on alpha 1-antitrypsin clearance.

Intestinal alpha 1-antitrypsin clearance in 6 healthy controls and 21 patients with Crohn's disease was measured simultaneously by two different methods. Faecal alpha 1-antitrypsin loss, determined conventionally by weight and alpha 1-antitrypsin concentration of the homogenized three day stool was compared with the faecal alpha 1-antitrypsin loss, which was calculated from weight of the three day stool sample and the mean alpha 1-antitrypsin concentration determined in three 1 g aliquots of the morning stool obtained at the three consecutive days during the collecting period. There was a significant correlation when comparing faecal alpha 1-antitrypsin loss (y = 0.96x + 10; r = 0.952) and intestinal alpha 1-antitrypsin clearance (y = 1.05x - 6.5; r = 0.974) measured by the different methods. Filling the aliquots by a standardized spoon into a vial prepared with a defined volume of solvent makes it possible to take a diluted, homogenized, and centrifuged stool sample out of the vial by the laboratory staff avoiding open faecal work up. The simplified method of measuring intestinal alpha 1-antitrypsin clearance permits to integrate the determination of enteric protein loss into routine diagnostics comparable to the faecal occult blood method.

Influence of rhein on rat colonic Na+,K+-ATPase and permeability in vitro.

Rhein, an aglucone of a laxative-acting anthraquinone, which induces net secretion in the human jejunum and colon, does not induce net secretion under open circuit current in in vitro conditions but reduces net absorption of electrolytes and water. In the stripped rat descending colon at a concentration of 2.10(-4) mol/l, the Na+, K+-ATPase is almost completely inhibited resulting in a decreased net absorption of electrolytes and water. There are no changes of the diffusional resistance of the paracellular pathway. Results point to a cellular mechanism of rhein by which absorption is inhibited so that physiological cellular secretion dominates. This does not rule out an additional activation of cellular secretion but net secretion can be explained solely by inhibition of absorption without the assumption of any additional secretory mechanism.

Postprandial cholylglycine serum concentration and extent of ileal inflammation or resection in Crohn's disease.

Postprandial cholylglycine serum concentration was determined in 45 resected and non-resected patients with Crohn's disease of the distal ileum. Cholylglycine serum concentration after meal stimulus in patients with ileal involvement of more than 30 cm was significantly lower than in controls and in patients with minor spread of inflammation. In patients with inflammation area less than 30 cm, there was a somewhat faster and higher increase and delayed decline of postprandial cholylglycine serum concentration. The present study shows that postprandial cholylglycine serum level gives a good estimate of the extent of ileal inflammation or resection.

Antiinflammatory treatment and intestinal alpha 1-antitrypsin clearance in active Crohn's disease.

Intestinal alpha 1-antitrypsin clearance was quantified in 17 patients with clinically active Crohn's disease before and after a six-week period of treatment with sulfasalazine and methylprednisolone. Before the study, alpha 1-antitrypsin clearance and, hence, enteric protein loss was elevated as being above control values in 16 patients. After therapy, clearance values decreased in 11 and were normalized in five patients. Serum albumin level was normalized in 11 of 12 patients who had hypoalbuminemia before the study. Clinical condition was improved in all but 1 patient after treatment. There was no close correlation between alpha 1-antitrypsin clearance and disease activity index. These results indicate that antiinflammatory therapy has a beneficial effect on enteric protein loss in Crohn's disease. The measurement of alpha 1-antitrypsin clearance provides a useful adjunctive technique in evaluating intestinal inflammatory activity, and it seems to be of use in following the efficacy of treatment in the course of illness in Crohn's disease.