Pro- and anti-inflammatory macrophages express a sub-type specific purinergic receptor profile.

Extracellular nucleotides act as danger signals that orchestrate inflammation by purinergic receptor activation. The expression pattern of different purinergic receptors may correlate with a pro- or anti-inflammatory phenotype. Macrophages function as pro-inflammatory M1 macrophages (M1) or anti-inflammatory M2 macrophages (M2). The present study found that murine bone marrow-derived macrophages express a unique purinergic receptor profile during in vitro polarization. As assessed by real-time polymerase chain reaction (PCR), Gαs-coupled P1 receptors A2A and A2B are upregulated in M1 and M2 compared to M0, but A2A 15 times higher in M1. The ionotropic P2 receptor P2X5 is selectively upregulated in M1- and M2-polarized macrophages. P2X7 is temporarily expressed in M1 macrophages. Metabotropic P2Y receptors showed a distinct expression profile in M1 and M2-polarized macrophages: Gαq coupled P2Y1 and P2Y6 are exclusively upregulated in M2, whereas Gαi P2Y13 and P2Y14 are overexpressed in M1. This consequently leads to functional differences between M1 and M2 in response to adenosine di-phosphate stimulation (ADP): In contrast to M1, M2 showed increased cytoplasmatic calcium after ADP stimulation. In the present study we show that bone marrow-derived macrophages express a unique repertoire of purinergic receptors. We show for the first time that the repertoire of purinergic receptors is highly flexible and quickly adapts upon pro- and anti-inflammatory macrophage differentiation with functional consequences to nucleotide stimulation.

How older patients' treatment preferences are influenced by disclosures about therapeutic uncertainty: surgery versus expectant management for localized prostate cancer.

OBJECTIVES: There is an ongoing debate about the proper management of localized prostate cancer in older men. We assessed whether older patients differ in their willingness to accept surgery versus expectant management for a hypothetical early stage, low grade, clinically localized prostate carcinoma, and whether patients' current levels or past history of urologic dysfunction (difficulties initiating urination, failing to empty the bladder, urinary dribbling, getting up at night to urinate, and frequency of sexual activity) influence their decisions. We assessed patients' willingness to choose surgery over expectant management by varying the expected survival benefit in years (ESBs-em) of surgery over expectant management. DESIGN: Structured interviews with a consecutive series of male patients. SETTING: A university-based Department of Veterans Affairs Medical Center. PATIENTS: One hundred forty-eight patients seen consecutively in General Medicine Clinic at the Department of Veterans Affairs Medical Center in Portland, Oregon, were enrolled in the study. Mean age of the patients was 66.3 years (SD = 10.3, range = 30-85); mean level of formal education was 12.6 years (SD = 2.7, range = 6-22). MEASUREMENTS: Patients were asked whether they would accept surgery or expectant management in one of 11 treatment comparisons. We varied the ESBs-em in 1-year increments from 0 years to 10 years. As described to patients, surgery carried a mortality risk at the time of treatment of 1 to 2%. Once any patient indicated a willingness to accept surgery at any of the treatment comparisons or if any patient reported preferring expectant management across all treatment comparisons, the elicitation procedure was stopped. All patients were asked to complete a urological and sexual functioning questionnaire to determine the presence of coexisting urological dysfunction and level of sexual activity both at present and in the past. RESULTS: Of the 148 patients enrolled in the study, 43.2% (64/148) preferred surgery with a zero expected life benefit over expectant management (ESBs-em = 0) and a 1 to 2% chance of dying within 1 month of surgery; 24.3% (36/148) rejected surgery as the expected life benefit of surgery was increased (0 < ESBs-em < or = 10 years); 26.4% (39/148) preferred expectant management even when there was a 10-year expected life benefit of surgery; 4.7% (7/148) preferred that their physician make the decision for them; and 1.4% (2/148) of patients reported that they preferred radiation therapy, an option that was not offered to them explicitly. Our results suggest that older patients are more likely to report a preference for expectant management (OR = 1.07). Further, our results suggest that patients who report current urinary dribbling (OR = 9.03) are much more likely to prefer expectant management but that this preference decreases with the amount of time they have had this problem. Similarly, we find that patients who have difficulty with starting urination are much more likely to prefer surgery (OR = 0.13), and this preference is also mediated by the number of years they have experienced this problem. Treatment choice was not associated with formal education, present health status, or the other urological symptoms we assessed. CONCLUSION: Our study in an older male veteran population showed preferences for a variety of options in prostate cancer. Although the majority of men preferred surgery, a significant number preferred expectant management. Our results show that preferences reflect patients' experiences with physical problems associated with disease and that these experiences need to be explored and considered by patients and their providers when making treatment decisions.

Older patients' willingness to trade off urologic adverse outcomes for a better chance at five-year survival in the clinical setting of prostate cancer.

OBJECTIVE: To assess whether patients report a willingness to trade-off urologic adverse outcomes--urinary incontinence and total impotence--for a better chance of 5-year survival in the clinical setting of prostate cancer; and, if so, whether patients' current levels of symptoms of urinary incontinence, impotence, and frequency of sexual activity influence their decisions. DESIGN: Structured interviews with a convenience sample of male patients. SETTING: A university-based Department of Veterans Affairs Medical Center. PATIENTS: One hundred sixty-three patients seen consecutively in General Medical Clinic at the Department of Veterans Affairs Medical Center in Portland, Oregon, were enrolled in the study. Mean age of the patients was 65.2 years (SD = 10.6, range - 35-84); mean level of formal education completed was 13 years (SD = 2.7, range = 5-19). MEASUREMENTS: In a hypothetical clinical setting of prostate cancer, patients were offered a choice of two procedures--Treatment A (surgery: worse short-term, better long-term survival) and Treatment B (radiation therapy: better short-term, worse long-term survival)--with varying benefit/risk trade-offs in time. Patients were presented with pairs of treatment curves that were developed from research data on survival for surgery versus radiation therapy for stage II prostate cancer confined to the prostate gland. Treatments were not identified to control for labeling effects. Patients were asked their willingness to accept a chance of immediate mortality for better 5-year survival in one of four treatment curve comparisons. Of those who accepted the net beneficial procedure, we then inquired as to whether urologic complications--urinary incontinence and wearing an appliance to collect urine or total impotence--altered the acceptability of that treatment. RESULTS: Ninety-four percent (153/163) of patients were willing to choose Treatment A (worse short-term, better long-term survival) on one of the four scenarios; the remainder (10/163) were unwilling to take Treatment A (worse short-term, better long-term survival) on any of the four scenarios. Sixty-two percent (95/153) of patients were willing to accept a 100% chance of urinary incontinence; 83% (127/153) were willing to accept a 100% chance of impotence (chi-square = 16.8 with 1 df, P = .0001). CONCLUSIONS: Our results in an older male veteran population suggest than many patients are more concerned with long-term survival in the clinical setting of prostate cancer than with short-term treatment risks. In addition, patients are more willing to accept an impotence outcome than a urinary incontinence outcome, but this result was not related to patients' reported frequency of sexual activity.

Patients' interpretations of verbal expressions of probability: implications for securing informed consent to medical interventions.

Physicians often use verbal expressions of probability to characterize their uncertainty about outcomes and the risks or side effects of proposed therapies. However, there is an extensive literature that documents the inherent vagueness of such expressions. Because of the potential importance of probability terms to physician-patient communication and decision-making, we asked patients to tell us the odds they thought applicable to the term "rare," as used by their physician to discuss the likelihood of an adverse outcome from surgery. Patients were randomly assigned to one of three outcome groups: death, severe heart attack, or severe pneumonia. Demographic data were elicited from each subject, as were indicators of present health status, medical history for certain diseases and surgery, and life expectancy. Linear regression and ANOVA analyses of the responses indicate that patient age, education level, perceived health status, and recency of experience with disease and medical care influence patients' numeric interpretations. We discuss the implications of these results.

How age, outcome severity, and scale influence general medicine clinic patients' interpretations of verbal probability terms.

OBJECTIVE: To assess whether the type of scale used (scaling effects) and the severity of outcome (outcome severity) influence patients' numerical interpretations of verbal probability expressions. DESIGN: Cross-sectional survey of patients in a general medicine clinic. SETTING: A university-based Department of Veterans Affairs Medical Center. PARTICIPANTS: 210 patients seen consecutively in a general medicine clinic. MEASUREMENTS AND RESULTS: The patients were randomized to scale and health outcome (complications of surgery). Two scales (a long form and a short form) were used to expressly allow patients to choose probabilities less than 1%. The long form had a lower bound of "< 1 out of 1,000,000"; the short form had a lower bound of "< 1 out of 1,000." Two complications were used: "death from anesthesia" and "severe pneumonia." In the context of being told that their surgeon believed that the chance the complication would occur was "rare," patients were asked to give the numerical estimate of that chance. The values elicited on both scales were significantly different for the two outcomes, with the "rare" risk of death from anesthesia being characterized as less likely than the "rare" risk of severe pneumonia (F = 5.24, p = 0.023). Linear regression and three-factor analysis of variance showed significant differences in the probabilities elicited for scale, outcome, and age, with older patients generally responding with higher probabilities than did younger patients. CONCLUSIONS: These findings suggest that the severity of the associated outcome and the scale used to elicit patients' numerical estimates of verbal probability expressions influence patients' quantitative interpretations of the verbal probability statement; and older patients respond with higher probabilities of negative outcomes than do younger patients. Future studies must continue to explore whether verbal probability expressions are adequate for communicating medical risk to patients or whether patients should be provided with numerical estimates of frequency.

[Adjustment to illness in patients with chronic physical diseases--initial experiences with the zurich illness adaptation questionnaire]. / Krankheitsverarbeitung von chronisch körperlich Kranken--erste Erfahrungen mit dem Zürcher Fragebogen zur Krankheitsverarbeitung (ZKV).

270 patients who suffered from gynaecological cancer, epilepsy or diabetes mellitus were examined with a newly developed questionnaire as to their coping behaviour. In order to assess the dimensions and reliability of the instrument, the data were evaluated by different statistical methods. For the three coping patterns established by factor analysis: anxiety/withdrawal, emotional neutrality/diversion and hope/facing of illness, significant correlations resulted with the variables age and sex. The outcome of the investigation suggests that if the disease takes a favourable turn, the chronically ill patient, similarly, copes with it in a favourable manner. For the differentiation and prominence of coping patterns, the patient's subjectively experienced impairment of his physical state of health seems to play an important role.

[Pre- and postoperative conditions in the self evaluation of 3 groups of surgical patients]. / Prä- und postoperative Befindlichkeit in der Selbstbeurteilung von drei Gruppen chirurgischer Patienten.

This article studies the self-assessed pre/postoperative course of the psychological condition of 3 patient groups (hernia, aorto-coronary bypass and cancer patients) and healthy controls. Some consequences for clinical work are discussed.