Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein.

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

[The competent cell - the immune system as a metaphor, sign, language and culture]. / Die kompetente Zelle - das Immunsystem als Metapher, Zeichen, Sprache und Kultur.

We investigated how the progressive function of the metaphor, the model world of signs, language and culture, link the cell's immunological knowledge with a perceivable concept of the body. Using ethnomethodologically oriented, partly interpretative text analysis, we examined the lymphocyte stimulation test, word clusters in immunology and other medical specialties, the linguistic presentation of the body in German, American and the internet, the presentation of the "self" of the cell in biology and immunology, and protocols of oncological out-patient interviews and chatrooms. When an abstract sign model is created, then the existence of a "negotiable", "competent" and "tolerant" immune cell is predominated by the concept of a cell and much less by elements of the body. Thus, the passive, spatial-anatomical concept of the body can be overcome and the position of the microscopically describable inner observer achieved. This is related to the American concept of a body that can be formed at will from animated individual parts. This model immune system impresses upon physical life and also provides a new metaphor for human interaction in accordance with the pattern of immunocompetent cells.

Disease-related worries and concerns: a study on out-patients with inflammatory bowel disease.

OBJECTIVE: To investigate the relationship between inflammatory bowel disease (IBD) patients' disease-related worries and concerns and their disease-related data, sociodemographic variables and perceived information level with respect to IBD. STUDY DESIGN: Prospective evaluation of disease-related concerns. SETTING: Out-patient IBD clinic of a university hospital. STUDY POPULATION: The study included 105 patients with IBD (72 with Crohn's disease and 33 with ulcerative colitis). MEASUREMENTS: Worries and concerns were measured using the standardized 25-item rating form of IBD patient concerns; actual disease activity was assessed by physicians using the Crohn's disease and clinical activity indices. Sociodemographic and other disease-related data were collected using a structured questionnaire. Patients' perceived information level was measured using a visual analogue scale. RESULTS: The issues of greatest concern to our patients were, in descending order of importance, having an ostomy bag (mean score +/- SD 63.6 +/- 38), the effects of medication (53.1 +/- 34), having surgery (51.6 +/- 36), the uncertain nature of the disease (46.5 +/- 32) and energy level (41.5 +/- 34). Patients with ulcerative colitis scored higher with respect to concern about loss of bowel control (P < 0.03). Disease-related worries and concerns correlated poorly with disease-related data (actual disease activity, severity of the course of IBD, diagnosis, disease duration or location, medication) but showed a significant negative correlation with patients' perceived information level about IBD (t = 0.2, P < 0.004). Lower information-level scores were associated with greater concerns. CONCLUSION: We conclude that the patients' information level about IBD and disease-related concerns have to be considered in clinical practice. Better information about IBD and psychosomatic counselling for patients who show high levels of concern may improve their quality of life and clinical care.

Lytic effector cell activity and major depressive disorder in patients with breast cancer: a prospective study.

The study examined lymphokine-activated killer cell (LAK) and natural killer (NK) cell activity in breast cancer patients prior to surgery as compared to effector cell lysis in patients with non-malignant breast tumors, further in connection with lifetime diagnosis of major depression, severity of current depression, anxiety and coping styles. Follow up studies covered a period of 6 and 12 months. Prior to surgery, life time diagnosis of major depressive disorder, trait anxiety and coping styles did not discriminate patients as far as effector cell lysis is concerned. LAK activity but not NK activity was reduced in patients with actual depressive symptoms (P < 0.01) and high state anxiety (P < 0.05). These findings support the hypothesis that LAK activity is a state marker of actually existing depression and anxiety prior to surgery. Affective rather than coping measures showed significant differences in LAK activity. For LAK activity, 1 year after surgery the only predicting factors were Tamoxifen therapy and chemotherapy.

A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control.

This paper reports the results of a prospective controlled trial of a program addressing reduction of onset distress and better future adaptation in adults who were enrolled at the time of diagnosis of type I diabetes mellitus. Patients were assigned randomly to either standard intensive treatment and patient education with the distress reduction program (N = 10) or to standard intensive treatment and patient education without this program (N = 13). Prospective follow-up of patients with multiple validated measures of treatment outcome showed less anxious coping behavior, less depression and less denial at the 9-month follow-up and less denial at the 15-month follow-up in the group with the distress reduction program, but no differences in metabolic control between the two groups at any time. We conclude that our program has a positive impact on the crisis at diabetes onset; the lower denial in the treatment group may lead to improved regimen adherence in the long term.

Psychological moderator variables and metabolic control in recent onset type 1 diabetic patients--a two year longitudinal study.

The relationships between psychosocial adjustment and subsequent glycaemic control were prospectively examined in forty-three adult patients during the first 2 yr after onset of type 1 diabetes mellitus. Decreasing depression was the single psychosocial parameter that changed over time. No correlations were found between the decrease in HbA1c levels and psychological variables at 8- and 16-month follow-ups. Global and specific coping features such as high control attitude, low coping anxiety and low emotional attribution correlated significantly with the decrease in HbA1c levels at the 2-yr follow-up, whereas stressful life events, depression, state-trait anxiety did not correlate. In a regression analysis coping explained 22% variance of the 2 yr decrease in HbA1c levels. We conclude that coping is a better predictor for metabolic control than emotional adaptation and life events. Metabolic control might deteriorate with prolonged stage of the disease being a first sign for psychophysiological coping exhaustion.

[Phase-specific function of denial in type 1 diabetic patients after disease onset]. / Zur phasenspezifischen Funktion der Verleugnung beim Typ 1 Diabetes Patienten nach Krankheitsausbruch.

In a longitudinal study we examined 43 patients with type 1 diabetes one week after onset as well as 8 and 24 month later in order to analyze the psychological role of denial processes in correlation to metabolic functions. Only depression decreased over the studied period while coping and denial remained stable. However, the adaptive function of denial after onset with low anxiety, good coping and few complaints became maladaptive over the first two years and the correlation of denial with a centripetal kinship behavior loosened. The destructive effect of denial was indicated only by delayed requests for assistance while no correlation could be shown for phase-specific internal restructuring of the psychological function of denial to compliance and metabolic control.

Hormonal and blood glucose responsiveness as an indicator of specific emotional arousal in type 1 diabetics.

The aim of the present study was to examine, whether individual emotional arousal induced by a specific stress interview may effect growth hormone (GH), cortisol, catecholamine and blood glucose levels in diabetes patients. To test the validity of this hypothesis we subjected 18 Type 1 diabetics and 18 healthy controls to a life event interview which produces individual arousal. During this stress interview catecholamines and plasma cortisol levels showed no significant increase, whereas there was a significant increase of GH over time in both group (p < 0.04), with a trend in diabetics to have a more marked GH response than controls (p < 0.10). Blood glucose levels remained unaffected by the interview. Depressed diabetics showed significantly higher cortisol increases (p < 0.004) than non-depressed diabetics, whereas there was no difference among depressed and non-depressed controls. Depression was not associated with an increase of other hormones or blood glucose levels in both groups. The results of our study confirm specific pathways in which individual emotional arousal and depression may lead to chronic metabolic disturbances as a result of GH and cortisol hypersecretion.

[Effectiveness of relaxation groups in patients with chronic respiratory tract diseases]. / Zur Effektivität von Entspannungsgruppen bei Patienten mit chronischen Atemwegserkrankungen.

In the long-term treatment of patients with chronic respiratory diseases, patient education contributes significantly towards improving the effectiveness of conventional drugs in the treatment of asthma-specific complaints and anxiety, as well as playing a role in improved disease coping. The aim of this study was to verify whether relaxation training programs undertaken subsequent to patient education may have an additional effect with regard to both medical and psychological variables. Relaxation training encompasses the basic exercises of autogenics, as well as exercises of functional relaxation. 49 patients participated in the relaxation group (22 male, 27 female). The mean age was 50.5 +/- 16.5 years. The control group used was made up of 37 patients with chronic respiratory diseases (17 male, 20 female) who had received asthma education, but no further therapeutic intervention. Prior to and immediately after the relaxation training, the following investigations were undertaken: lung function, patient diary, Spielberger anxiety scale, Giessen list of complaints (modified and augmented) and Ziegler coping questionnaire. The linear rating scale model was used for measuring changes. The following significant changes were observed in the relaxation group as compared with the control group: decrease of trait fear, alleviation of asthma-specific complaints and asthma attacks, decrease in sleep disturbances and in morning coughing urge, reduction in the required quantities of controlled-dosage aerosol, and a modified attitude toward the disease in the sense of an improved subjective coping competence.(ABSTRACT TRUNCATED AT 250 WORDS)

[Glycosylated hemoglobin and diabetes--self monitoring (compliance) in depressed and non-depressed type I diabetic patients]. / Glykosyliertes Hämoglobin und Glukose--Selbstmonitoring (Compliance) bei depressiven und nicht depressiven Typ I-Diabetikern.

128 type I diabetics were examined in view of connections between psychosocial factors and metabolic control. Indications of a direct interaction between depressivity, incidence of complaints and the level of hyperglycemia were found. The prevalence of manifest depression ranges at a total of 25 percent. The results further show connections between coping with the disease and behavior. High recording frequency, frequent measurements and medical consultations are found in active coping. Changes in relations to close persons and frequent change of job are psychosocial effects of the disease manifesting themselves in poorer metabolic control. In conclusion, high-risk groups of depressive diabetes patients and those under particular stress are defined.

[Effect of structured ambulatory training of patients with chronic respiratory tract diseases on the efficiency of long-term care]. / Einfluss einer strukturierten ambulanten Schulung von Patienten mit chronischen Atemwegserkrankungen auf die Effizienz der Dauerbehandlung.

In spite of the availability and widespread use of a number of effective medications, the frequency of severe attacks of asthma bronchiale including those with fatal outcome has not decreased. One possible reason for this is the delay in therapeutic intervention of up to 30 minutes resulting either from transport time to a hospital or from the response time of mobile ambulance services. Treatment delays are also frequent co-factors for decreased well-being in non-emergency cases. Prompt initiation of countermeasures, regardless of time or place, can only be guaranteed when the patient himself is capable of carrying them out with the same expertise as his attending physician. Toward this end, a model patient-training program was investigated. The didactic goal of the training was to make the patient an expert in his chronic disease. The medical goal of the training was to improve the quality of a complex long-term therapy and with it, the patient's well-being and quality of life. The content of the training corresponded largely to that contained in a lecture series for medical students or physicians on the same subject. Style and choice of words (avoidance or explanation of medical terminology) was of course adapted to the lay-status of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[The significance of psychosocial complaints in the initial interview--a study of unselected patients of an internal medicine/polyclinic university ambulatory service]. / Die Bedeutung psychosozialer Beschwerden in der Erstanamnese--eine Untersuchung an unselektierten Patienten einer internistisch/poliklinischen Universitätsambulanz.

In clinical practice one is repeatedly confronted with patients, who report psycho-social problems during the first interview. In this study 128 patients have been examined in the outpatient clinic at the Department of Medicine 1 of the University Hospital in Vienna. The most important issue investigated was to clarify whether or not the psycho-social complaints expressed at the initial interview could be correlated with either functional disorders or somatic disease. Further we tried to determine whether or not the complaints influenced the course of the disease and gave any indication for the presence of a depressive disorder or complicated a somatic disorder by additional psychosomatic complaints. Our results indicate that the expression of psycho-social problems indeed correlates with stronger psychosomatically conditioned body dysfunctions, but do not sufficiently explain whether or not functional disease can be expected. However, the reported psycho-social problems result in a stronger inclination towards depressive mood and lead the patient to his/her own explanation how the illness has developed. Both facts are of importance for the patient-physician relationship and constitute an integral part of the (non-)compliance.

[Coping with illness in rheumatoid arthritis]. / Krankheitsbewältigung bei der rheumatoiden Arthritis.

Rheumatoid arthritis, a lifelong chronic disease, creates serious psychosocial as well as medical problems. We investigated coping with rheumatoid arthritis in 50 patient. The examination of coping-strategies used by R. A.-patients seems to show no fundamental difference to the coping behavior of patients with other chronic diseases. Biomedical conditions of the disease (Rheumafactor sero-positiv, sero-negativ) are related to different coping-strategies. Patient without psychiatric problems have a better medical health condition and, compared to depressive R. A.-patient prefer more active and optimistic coping. However, the context between psychological well-being and health (before the onset of R. A.), coping, adjustment to illness, and course of the illness is unclear.

[Integration of psychosomatics with internal medicine. A diagnostic and therapeutic strategy for psychosomatic-internal medicine patients]. / Die Integration der Psychosomatik in die internistische Klinik. Eine diagnostische und therapeutische Strategie bei psychosomatisch-internistischen Patienten.

The high incidence of contributory psychosocial factors in developmental aspects of internal diseases makes it necessary to give up traditional forms of cooperation between internal and psychosomatic medicine, such as consultations, in favour of more intensive cooperation, in the course of which psychosocial aspects would be taken more into account in diagnosis and therapy of all patients in medical wards and clinics. A new method of treatment integrated into the medical department is presented, which favours not only patients, but also team-centered approach. The referral frequency of the new service, the diagnostic distribution and the therapeutic management of the first 270 patients is discussed. Special staff training, the key function of the first interview, the attainable cooperation and pre-selection of referred patients and the importance of the referral talk are emphasized.