Companion animals in palliative care: a hidden quality option?

In the light of the unprecedented demographic changes in many countries it is important to review and adapt existing strategies for giving old and incurable patients the adequate health care. Based on available data the importance of companion animals needs to be considered as part of individual care planning. Despite intensive research in other areas of health care, there is limited data concerning the use of companion animals in palliative care. The field demands much more recognition. For many people companion animals can be a chance for better quality of life.

[Psychosocial support care wanted and actually received by patients with cancer. Gender-specific differences]. / Psychosoziale Unterstützungswünsche und tatsächlich erhaltene Versorgung onkologischer Patienten. Geschlechtsspezifische Unterschiede.

BACKGROUND AND OBJECTIVES: Professional psychosocial support of patients with cancer is an essential component of the entire process of medical care of these patients. But so far gender specific differences have only rarely been investigated. Yet some studies have suggested that there are differences between male and female patients regarding their psychological burden and their use of psychosocial support facilities. This article discusses the latter issue, based on empirical data. METHODS: At the beginning of their treatment (t1) the patients were asked to answer a questionnaire exploring their needs and wishes regarding medical and psychological care, as well as regarding self-support. There were 252 patients (60% males; mean age of males = 60.1 ; mean age of females = 55.5) with different kinds of cancer (39.7% of males had prostate cancer; 26.7% of females had breast cancer). The follow-up (t2) took place half a year after t1. As part of the follow-up questionnaire data regarding the meeting of the individual patient's needs was collected. Standardized scales were used (t1, t2), as well as a clinical interview (SKID) (t1), which recorded psychological co-morbidity. RESULTS: The need for support was found not to differ significantly between the genders but depended on the grade of co-morbidity and on the particular group of supporting professionals, respectively. Most frequently, within the overall condition "medical support" the patients' need for support (t1) and the actually received support (t2) were found to be coincident (85.7 - 94.2 %) for women as for men. Particularly with regard to psychological and social care, multivariate analysis revealed the need for care (t1) being a predictor of actually received support (t2). Especially within the group of women the factor "living alone" was found to explain the congruence between the need for care and the received support. CONCLUSION: Few gender-specific differences regarding need for care and actually received support have been found within this cohort of male and female patients with cancer. It is a unclear to what degree such differences could be due to the design of the study. It is important to assess the patient's wishes and needs for multiprofessional care at the beginning of cancer treatment. In addition the family and social situation must be taken into account.

Dobutamine stress cardiovascular magnetic resonance at 3 Tesla.

PURPOSE: The assessment of inducible wall motion abnormalities during high-dose dobutamine-stress cardiovascular magnetic resonance (DCMR) is well established for the identification of myocardial ischemia at 1.5 Tesla. Its feasibility at higher field strengths has not been reported. The present study was performed to prospectively determine the feasibility and diagnostic accuracy of DCMR at 3 Tesla for depicting hemodynamically significant coronary artery stenosis (> or = 50% diameter stenosis) in patients with suspected or known coronary artery disease (CAD). MATERIALS AND METHODS: Thirty consecutive patients (6 women) (66 +/- 9.3 years) were scheduled for DCMR between January and May 2007 for detection of coronary artery disease. Patients were examined with a Philips Achieva 3 Tesla system (Philips Healthcare, Best, The Netherlands), using a spoiled gradient echo cine sequence. Technical parameters were: spatial resolution 2 x 2 x 8 mm3, 30 heart phases, spoiled gradient echo TR/TE: 4.5/2.6 msec, flip angle 15 degrees . Images were acquired at rest and stress in accordance with a standardized high-dose dobutamine-atropine protocol during short breath-holds in three short and three long-axis views. Dobutamine was administered using a standard protocol (10 microg increments every 3 minutes up to 40 microg dobutamine/kg body weight/minute plus atropine if required to reach target heart rate). The study protocol included administration of 0.1 mmol/kg/body weight Gd-DTPA before the cine images at rest were acquired to improve the image quality. The examination was terminated if new or worsening wall-motion abnormalities or chest pain occurred or when > 85% of age-predicted maximum heart rate was reached. Myocardial ischemia was defined as new onset of wall-motion abnormality in at least one segment. In addition, late gadolinium enhancement (LGE) was performed. Images were evaluated by two blinded readers. Diagnostic accuracy was determined with coronary angiography as the reference standard. Image quality and wall-motion at rest and maximum stress level were evaluated using a four-point scale. RESULTS: In 27 patients DCMR was performed successfully, no patient had to be excluded due to insufficient image quality. Twenty-two patients were examined by coronary angiography, which depicted significant stenosis in 68.2% of the patients. Patient-based sensitivity and specificity were 80.0% and 85.7% respectively and accuracy was 81.8%. Interobserver variability for assessment of wall motion abnormalities was 88% (kappa = 0.760; p < 0.0001). Negative and positive predictive values were 66.7% and 92.3%, respectively. No significant differences in average image quality at rest versus stress for short or long-axis cine images were found. CONCLUSION: High-dose DCMR at 3T is feasible and an accurate method to depict significant coronary artery stenosis in patients with suspected or known CAD.

[Prevalence of concomitant psychiatric disorders and the desire for psychosocial help in patients with malignant tumors in an acute hospital]. / Häufigkeit psychischer Begleiterkrankungen und der Wunsch nach psychosozialer Unterstützung bei Tumorpatienten im Akutkrankenhaus.

BACKGROUND AND OBJECTIVE: A diagnosis of cancer can overpower a patient's ability to cope and thus can increase the prevalence of psychiatric disorders in this group of patients. It was the aim of this study to estimate that prevalence in tumor patients during their acute treatment. PATIENTS AND METHODS: 689 patients with malignancies were interviewed using the structure clinical interview connected with the Diagnostic and Statistical Manual of Mental Disorders IV [SCID]) DSM-IV during their first days of inpatient treatment. The patients' wishes for psychosocial support by the oncological team were assessed. RESULTS: 32 % of the patients were diagnosed having a psychiatric disorder, e. g. depression. Prevalence was greater among female and/or young patients, those who had little money, were receiving chemotherapy and those who had not yet been diagnosed with cancer but in whom it was suspected. Some types of tumor were more likely to be associated with a mental disorder, for instance gynecological and head-and-neck malignancies. 83 % of the patients asked for psychosocial help from the treating physician, 44 % from the social worker, 30 % from the clinical psychologist, and 8 % from a spiritual adviser. Support was especially needed by patients who felt sad or depressed, and in those who lacked social support: these needs were unrelated to tumor stage and time since diagnosis. CONCLUSIONS: Inpatient cancer patients frequently suffer from a psychiatric disorder. The majority of them would like to get psychosocial support, especially from their treating physician. It should be recognized that it is not only palliative care patients with advanced disease who need psychosocial treatment and support.

CD44-v6 concentrations in carcinoma of the uterine cervix: lack of prognostic significance.

Several kinds of cellular adhesion molecules, like different splicing variants of CD 44, have gained important as prognostic or markers for metastatic disease. Fresh frozen samples from 64 cervical carcinoma (CX) were stored in liquid nitrogen and examined using ELISA-technique, testing the prognostic impact. Normal cervical tissue served as control. CD 44-v6 concentration, was significant elevated in tumor tissue, when compared to the controls (P=0.04). There was no correlation to tumor stage (P=0.61), lymphovascular space involvement (P=0.075) or pelvic lymph node involvement (P=0.81). The CD 44-v6 concentration was not informative regarding recurrence-free and overall survival. Contrary to immunohistochemistry, the quantification of CD 44-v6 using ELISA-technique does not provide any further information.

CYP3A4, CYP2C9 and CYP2B6 expression and ifosfamide turnover in breast cancer tissue microsomes.

Ifosfamide is a prodrug that requires bioactivation by cytochrome P450 for antitumour activity. Up to now, little is known, to what extent in addition to the liver the ifosfamide metabolism may occur intratumorally. For this purpose, we investigated the expression of CYP3A4, CYP2C9 and CYP2B6 in breast cancer tissue using Western Blotting. Ifosfamide turnover was determined by detection of metabolites of the ifosfamide 4-hydroxylation and N-dechloroethylation in tumour microsomal incubations using HPLC/UV and LC/MS. The results demonstrate that all mammary tumours (n=11) reveal CYP3A4 expression; contents varied from 0.5 to 63 pmol mg(protein)(-1). CYP2C9 (n=9) was present in all tested breast tumour samples, too, while CYP2B6 (n=10) protein could not be detected. All measured breast cancer microsomes (n=4) showed an ifosfamide N-dechloroethylation capacity in the range from 0.04 to 0.21 pmol min(-1) mg(protein)(-1), while metabolites of the 4-hydroxylation could not be determined. In conclusion, the detected presence of CYP3A4 and CYP2C9 in breast tumours offers the possibility of intratumoral turnover of ifosfamide. For the first time in the literature, we could demonstrate a turnover of ifosfamide by microsomal preparations from human breast cancer tissue. A calculated modulation of intratumoral ifosfamide turnover could considerably influence its therapeutic efficiency.

Clinical relevance of urokinase-type plasminogen activator and its inhibitor type 1 (PAI-1) in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The expression of uPA and PAI-1 as parameters of tumour-associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process. However, there is limited information on the impact of these parameters in cervical carcinoma. METHODS: Quantitative levels for uPA (n = 114) and PAI-1 (n = 103) were researched in operatively treated, surgically staged squamous cell cancer of the uterine cervix, using an ELISA-technique. Results were assessed regarding their impact in predicting pelvic lymph nodes metastases, tumour recurrence rate and recurrence free survival (RFS) using uni- and multivariate analysis. RESULTS: Median levels of both parameters were significantly higher in tumour tissue than in normal cervical tissue (p < 0.001). Detection of uPA gave no useful prognostic information. PAI-1 concentration showed a positive correlation with advanced tumour stage (p = 0.008), but no significant correlation with nodal status (pN0: 2.6 vs. pN1: 4.0 ng/mg protein; p = 0.092). Using a cut-off level of 2.4 ng/mg protein, patients with elevated PAI-1 levels demonstrated reduced RFS (45.9 versus 52.9 months; p = 0.1). Multivariate analysis, including nodal status, tumour stage, lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI-1. CONCLUSIONS: The results indicate, that PAI-1 expression is of some prognostic impact in cervical cancer, indicating an association of elevated PAI levels with local tumour progression and reduced recurrence-free survival.

MRI measurement of wall shear stress vectors in bifurcation models and comparison with CFD predictions.

Steady fluid flow was studied in a simple bifurcation model and in a physiologically realistic model of the human carotid bifurcation. Wall shear stress (WSS) vectors were calculated from phase-contrast (PC) magnetic resonance imaging (MRI) measurements of the velocity field. Velocity measurements in the inflow regions were also used as boundary conditions for computational fluid dynamics (CFD) calculations of WSS, which were compared with those derived from MRI alone. In regions of well-behaved flow, MRI and CFD estimates of WSS were in good general agreement. In regions of disturbed flow, for example near the bifurcation, the quality of the MRI measurements was sufficient for reliable calculation of WSS vectors when a sensitive surface coil was used. The combination of MRI and CFD would seem to be a powerful technique for the investigation of flow phenomena.

Evidence of leptin expression in normal and polycystic human ovaries.

Leptin, the 'obese' protein, is found in cultured granulosa cells derived from human pre-ovulatory follicles. However, the occurrence of leptin has not been studied in intact ovaries, either normal or polycystic, until now. Paraffin sections from 25 human ovaries of different cycle stages and 25 wedge resections of polycystic ovaries were investigated by means of immunochemistry. Additionally, three ovaries were available for reverse transcription-polymerase chain reaction analysis. Leptin-positive cells were located in the granulosa cells of pre-antral follicles, and distinctly in the thecal layer of intact and regressing antral follicles. In the corpus luteum (CL) in the developmental stage, the former epithelioid leptin-positive thecal cells became fibroblast-like in the septum. In the CL of the secretory stage, single leptin-positive cells were detected between luteal cells. In polycystic ovaries, leptin-positive cells were noted both in the hypertrophied thecal layer and in the luteinized granulosa layer. Our findings on leptin expression at the protein level were confirmed by a positive mRNA signal for leptin in granulosa cells and in the CL. Additionally, mRNA of the full-length leptin receptor OB-R and of the short isoforms B219.1-B219.3 was identified in granulosa cells and the CL, as well as in the cortex and medulla. We conclude that leptin is produced in the ovary and may act in autocrine and paracrine ways.

Quantitative analysis of PC MRI velocity maps: pulsatile flow in cylindrical vessels.

The accuracy of MR phase contrast (PC) velocity mapping, and the subsequent derivation of wall shear stress (WSS) values, has been quantitatively assessed. Using a retrospectively gated PC gradient-echo technique, the temporal-spatial velocity fields were measured for pulsatile flow in a rigid cylindrical vessel. The experimental data were compared with values derived from the Womersley solution of the Navier-Stokes equations. For a sinusoidal waveform, the overall root-mean-square (rms) difference between the measured and analytical velocities corresponded to 13% of the peak fluid velocity. The WSS derived from the data displayed a 14% rms difference with the analytical model. As an example of a more complicated flow, a triangular saw-tooth waveform was deconstructed into its Fourier components. Velocity maps and the WSS were calculated by the superposition of the individual solutions, weighted by the Fourier series coefficient, for each harmonic. The velocity and experimentally derived WSS agreed with the analytical results (4% and 12% rms difference, respectively). Evaluation of the analytical models allowed an estimate of the inherent accuracy in the measurement of velocity maps and WSS values.

CD44 mediates constitutive type I receptor signaling in cervical carcinoma cells.

OBJECTIVE: The CD44 transmembrane glycoprotein family has been implicated in the growth and metastasis of numerous human cancers. CD44 may function in some cells through interactions with type I receptor tyrosine kinases, including erbB2. Here, we tested whether CD44 interacts with erbB2 and another type I receptor, the epidermal growth factor receptor (EGFR), in human cervical carcinoma tissues and cell lines and whether these interactions influence erbB2 signaling. METHODS: CD44, EGFR, and erbB2 colocalization were examined in 36 pT1b-pT2b cervical cancer cases and in the CaSki and SiHa cervical carcinoma cell lines by immunohistochemistry and laser scanning confocal microscopy. The role of CD44-EGFR-erbB2 interactions in erbB2 signaling was examined by immunoprecipitation and using antisense CD44 oligonucleotides. RESULTS: CD44, erbB2, and EGFR coexpression and colocalization were observed in 42% (15/36) of cervical carcinoma cases and in both cervical carcinoma cell lines. Colocalization occurred to an equivalent extent in all tumor grades examined. CD44 coimmunoprecipitated with erbB2 and EGFR in cervical carcinoma cell lysates, indicating that these proteins interact with each other. Reduction of CD44 expression inhibited constitutive erbB2 activity. High CD44 expression was linked to EGFR activity using dominant negative EGFR, suggesting that type I receptors may autoregulate their activity in these cells. CONCLUSIONS: Our data indicate that CD44 can mediate type I receptor function in cervical carcinoma cells that overexpress both CD44 and either erbB2 or EGFR and suggest a novel mechanism by which these proteins may contribute to cervical carcinoma tumor growth and metastasis.

Mutational analysis of the PRL receptor gene in human breast tumors with differential PRL receptor protein expression.

PRL is a major growth and differentiating hormone in the human breast, with activation of the PRL-PRL receptor complex increasingly recognized as an important mechanism in the induction and progression of mammary tumors. Although constitutive activation of various hormone and growth factor receptors is newly recognized as a common cause of tumor development, the PRL receptor gene has not been analyzed for similar aberrations in breast and other tumors. Therefore, using bacterial artificial chromosomes containing the PRL receptor gene and intron-spanning PCR, we determined the exon-surrounding intron sequences providing primers for the first analysis of the entire coding region of the human PRL receptor gene. We examined the presence of PRL receptor in 41 breast tumors by immunohistochemistry and attempted a correlation of its expression to pathological grading of the disease. Then tumor cells were isolated by laser capture microdissection to examine DNA from 30 patients for PRL receptor mutations. The PRL receptor immunoreactive score did not correlate to the tumor size, histopathological grading, age, or family history of patients. PRL receptor immunoreactivity was predominantly found in steroid hormone receptor-positive tumors, but without overall correlation of immunoreactive score. In both PRL receptor-positive and PRL receptor- negative breast cancer cells, direct sequencing of the coding sequence of the PRL receptor gene did not detect any somatic or hereditary gene aberrations. In conclusion, PRL receptor mutations do not appear to be common in human breast cancer, suggesting that constitutive activation of the PRL receptor can be excluded as a major cause of mammary tumor genesis. The molecular structure of the PRL receptor seems to remain intact in tumor tissue, and systemic and local production of PRL may participate in tumor cell growth and proliferation through functional receptors.

Physiological flow waveform in a rigid elliptical vessel.

A procedure to model the velocity and wall shear stress for a physiological flow in a non-cylindrical vessel is presented. The work describes how a vessel with an elliptical cross section may be used to represent flow in compressed or partially occluded arteries and veins. The procedure was applied to produce a simulation of a physiological flow in a straight rigid vessel with a slightly elliptical cross section (ellipticity, epsilon = 0.8). Fourier analysis was performed on a physiological flow waveform. Flow in the common carotid artery was satisfactorily represented (Pearson correlation coefficient, r > 95%) with a series of five harmonic terms. Expressions involving a linear combination of ordinary and modified Mathieu functions were used to describe the velocity and wall shear stress for each harmonic. An outline of the procedure, and the expressions, which were used to compute the characteristic Mathieu numbers and coefficients is illustrated with their behaviour at the fundamental and Nyquist frequencies. Superposition of the individual contributions to the velocity and wall shear stress allowed the calculation of the overall properties of the flow.

[Patient-ventilator interaction during noninvasive pressure supported spontaneous respiration in patients with hypercapnic COPD]. / Interaktion von Patient und Ventilator während nichtinvasiver druckunterstützter Spontanatmung bei Patienten mit hyperkapnischer COPD.

BACKGROUND: Noninvasive pressure support ventilation (NPSV) demands triggering with each breath. This study investigates the effects of NPSV via face mask on breathing pattern, ventilation and respiratory muscle loading in patients with hypercapnic stable COPD. METHODS: 7 patients (age 66 +/- 9 years; FEV1 43 +/- 13% predicted; PaO2 52 +/- 19 mmHg; PaCO2 58 +/- 12 mmHg) were included. The physiologic variables were evaluated during spontaneous breathing and at the end of a 60 minutes period with NPSV. Inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) were adjusted to 12-14 cm H2O and 3 cm H2O, respectively. Respiratory muscle activity was measured as esophageal and transdiaphragmatic pressure time product (PTPes and PTPdi). RESULTS: Non-triggering was observed only occasionally. Compared to unsupported spontaneous breathing NPSV improved ventilation: PaCO2 was reduced from 58 +/- 11 mmHg to 50 +/- 14 mmHg (p +/- 0.05). Respiratory muscles were unloaded by 30% (p +/- 0.05). Breathing frequency and breathing pattern did not change. CONCLUSIONS: In patients with hypercapnic stable COPD NPSV effectively recognizes and supports breathing efforts. As a result ventilation is improved and respiratory muscles are unloaded.

Flow in elliptical vessels calculated for a physiological waveform.

Understanding the nature of pulsatile flow is an important issue in haemodynamics, especially the initiation and progression of vascular disease. The geometry of a non-circular vessel was idealised to an elliptical cross-section, and the dynamic properties of the flow were calculated for a physiological waveform. The Fourier harmonics for a common carotid waveform were determined, and the velocity profile and wall shear stress were calculated from the superposition of the individual contributions from each harmonic. The effects of ellipticity on the flow pattern were found to be significant. The velocity profile along the major axis of the elliptical cross-section developed a flattened peak, which widened as the vessel became more elliptical. Wall shear stress demonstrated an angular dependence in elliptical vessels, where the point of minimum shear stress was located at the end of the major axis. Comparison with a cylindrical vessel demonstrated a 3% decrease in peak wall shear stress (tau = 2.96, N.m(-2)) at the end of the major axis, and 10% in the mean wall shear stress (tau = 0.44 N. m(-2)), for an elliptical vessel (epsilon = 0.8). The temporal average wall shear stress, which has been associated with atherogenic sites, also displayed a minimum at the end of the major axis that decreased with more elliptical cross-sections.

Auditory behaviour of a parasitoid fly (Emblemasoma auditrix, Sarcophagidae, Diptera).

Females of the parasitoid fly Emblemasoma auditrix find their host cicada (Okanagana rimosa) by its acoustic signals. In laboratory experiments, fly phonotaxis had a mean threshold of about 66 dB SPL when tested with the cicada calling song. Flies exhibited a frequency dependent phonotaxis when testing to song models with different carrier frequencies (pulses of 6 ms duration and a repetition rate of 80 pulses s(-1)). However, the phonotactic threshold was rather broadly tuned in the range from 5 kHz to 11 kHz. Phonotaxis was also dependent on the temporal parameters of the song models: repetition rates of 60 pulses s(-1) and 80 pulses s and pulse durations of 5-7 ms resulted in the highest percentages of phonotaxis performing animals coupled with the lowest threshold values. Thus, parasitoid phonotaxis is adapted especially to the temporal parameters of the calling song of the host. Choice experiments revealed a preference of a song model with 9 kHz carrier frequency (peak energy of the host song) compared with 5 kHz carrier frequency (electrophysiologically determined best hearing frequency). However, this preference changed with the relative sound pressure level of both signals. When presented simultaneously, E. auditrix preferred 5-kHz signals, if they were 5 dB SPL louder than the 9-kHz signal.

Reduction of electromagnetic interference from a commercially available MR-compatible flow simulator.

Electromagnetic interference (EMI) associated with the electronics of a commercially available computer controlled flow simulator substantially decreases the quality of the MR image. The effect of a custom-built radiofrequency shield on its spectral emission, and the corresponding signal-to-noise ratio measured for the image of a standard phantom, were determined. The results demonstrate the elimination of EMI and a significant improvement in image quality.

[Dose intensified adjuvant chemotherapy in high risk breast carcinoma with 4-9 positive lymph nodes]. / Dosisintensivierte adjuvante Chemotherapie beim Hochrisikomammakarzinom mit 4-9 positiven Lymphknoten.

OBJECTIVE: Taxanes and anthracyclines represent the two most active groups of agents for the treatment of breast cancer. We evaluated this combination in patients with more than 3 positive lymph nodes in an adjuvant, dose-intensive, sequential therapy in comparison with the standard chemotherapy regimen epirubicin/cyclophosphamide in relation to toxicities. MATERIAL AND METHODS: Since 9/96 127 patients with 4-9/over 9 positive lymph nodes have been recruited from 21 participating centers in an ongoing trial. 67 patients were prospectively randomised for first-line chemotherapy to treatment group A (epirubicin 90 mg/m2-paclitaxel 175 mg/m2; 4 cycles bi-weekly, supported by G-CSF 5 micrograms/kg day 5-13 and 3 sequential cycles of CMF 600/40/600 mg/m2 at 2-weeks interval) and 60 patients to treatment group B (epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2, 4 cycles tri-weekly, and 3 sequential cycles of CMF 600/40/600 mg/m2 at 3-weeks interval). RESULTS: Preliminary safety and toxicity data are evaluable for 679 cycles. Data about response rate and disease-free-survival and overall survival will be delivered later. For the hematological toxicity the main grade 3 and 4 adverse events for A vs. B were: leucopenia 9.8% vs. 8.4%, febrile neutropenia 1.6% vs. 0.8%--anemia (< 5.9 mmol/l), 0.4% vs. 0.2%--thrombopenia 0% vs. 0%. Non-hematological toxicity occurred more frequently in group A (grade 2, 3, 4):--neuropathy 4.4% vs. 0%,--nausea/emesis 27.8% vs. 19.3%,--fatigue 14.6% vs. 3.4% and mucositis 2.8% vs. 0.3%.