Incidence of osteoradionecrosis after combined radiotherapy-chemotherapy of head and neck tumors

Combined modality therapy, consisting of radiation, chemotherapy and surgery are used to treat primary tumours aiming to preserve function and increase tumour control. In the present prospective trial 112 patients underwent combined preoperative radio-chemotherapy, 35 patients were treated with combined radio-chemotherapy as only treatment. At a median follow-up of 26 months eight patients (2.8%) have developed an osteo-radionecrosis, which is comparable with data from the literature. When known risk factors are avoided the incidence of osteo-radionecrosis is not increased following combined therapy. The most important factors for development of osteo-radionecrosis following radio-chemotherapy are large tumours and tumour infiltration in the mandible.     

Increasing the thermal enhancement ratio by simultaneous application of radiation and hyperthermia--technical possibilities in interstitial application

Whereas the cytotoxic effect of hyperthermia is independent and without any time relationship with the radiation treatment, the heat induced radiosensitization only appears with simultaneous application of radiation and heat. Although the highest thermal enhancement ratio (TER) can be achieved with simultaneous application this protocol is not used in clinical practise because of technical problems. From a practical point of view the major effect of a non simultaneous application will have to rely on hyperthermic cytotoxicity. A two-zone needle which offers the possibility to conduct radiation and heat simultaneously in order to confine this to a three-dimensional radiation and heat is described.     

Qualitätssicherung in der Therapie chronischen Schmerzes

The present paper is one of a series of publications, reviewing German instruments for psychological assessment of pain. Their main focus is on the results of a task force on quality testing for each subject. This paper describes and comments on methods regarding self-reporting of pain cognitions and both cognitive and behavioral strategies for coping with pain. Concerning pain cognitions one focus is on patients' attributions of causes of pain and the modes of controlling pain (subjective pain model). The other focus is on instruments recording "pain beliefs" in the sense of dysfunctional congitions associated with the experience of pain. Each instrument was examined with reference to approved psychometric criteria, empirical foundation and clinical relevance. It was noted that several instruments are deficient in their psychometric criteria and their empirical foundations. We used these data as a basis to elaborate a specific and differential recommendation. A similar procedure was followed with instruments for the assessment of pain-related coping strategies. According to our research there are two subgroups of coping instruments, one more specifically for cognitive coping with pain, and the other combined with behavioral coping strategies. Once again, we elaborated a specific and differential recommendation, giving priority to instruments taking account of both cognitive and behavioral dimensions of coping with pain.     

The Feeding of Alcohol in Liquid Diets: Two Decades of Applications and 1982 Update

The technique of feeding ethanol as part of a totally liquid diet was invented two decades ago and its successful application for the intervening period is reviewed. This technique results in much higher ethanol intake than with conventional procedures. As a consequence, various complications observed in alcoholics were reproduced in animal models, including fatty liver, hyperlipemia, various metabolic and endocrine disorders, tolerance to ethanol and other drugs, physical dependence and withdrawal, the fetal alcohol syndrome and, in the baboon, liver fibrosis and cirrhosis. Variations of the liquid diet formulation are compared and three standardized basic formulas are being proposed for the rat: (1) a regular diet, comparable to the diet previously referred to as the "Lieber-DeCarli Formula" and suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of liver changes characterized by a fatty liver; (2) a low fat diet comparable in all respects to the preceding diet but with a lower fat content, intended to minimize the hepatic changes; and (3) a high protein formula particularly useful in those circumstances in which an oversupply of dietary protein might be recommended (i.e., pregnancy and lactation) .     

Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion

Natural antibodies are produced at tightly regulated levels in the complete absence of external antigenic stimulation. They provide immediate, early and broad protection against pathogens, making them a crucial non-redundant component of the humoral immune system. These antibodies are produced mainly, if not exclusively, by a subset of long-lived, self-replenishing B cells termed B-1 cells. We argue here that the unique developmental pattern of these B-1 cells, which rests on positive selection by self antigens, ensures production of natural antibodies expressing evolutionarily important specificities that are required for the initial defense against invading pathogens. Positive selection for reactivity with self antigens could also result in the production of detrimental anti-self antibodies. However, B-1 cells have evolved a unique response pattern that minimizes the risk of autoimmunity. Although these cells respond rapidly and strongly to host-derived innate signals, such as cytokines, and to pathogen-encoded signals, such as lipopolysaccharide and phosphorylcholine, they respond very poorly to receptor-mediated activation. In addition, they rarely enter germinal centers and undergo affinity maturation. Thus, their potential for producing high-affinity antibodies with harmful anti-self specificity is highly restricted. The positive selection of B-1 cells occurs during the neonatal period, during which the long-lived self-renewing B-1 population is constituted. Many of these cells (B-1a) express CD5, although a smaller subset (B-1b) does not express this surface marker. Importantly, B-1a cells should not be confused with short-lived anergic B-2 cells, which originate in the bone marrow in adults and initiate CD5 expression and programmed cell death following self-antigen recognition. In summary, we argue here that the mechanisms that enable natural antibody production by B-1 cells reflect the humoral immune system, which has evolved in layers whose distinct developmental mechanisms generate complementary repertoires that collectively operate to maximize flexibility in responses to invading pathogens. B-2 cells, present in what may be the most highly evolved layer(s), express a repertoire that is explicitly selected against self recognition and directed towards the generation of high-affinity antibody response to external antigenic stimuli. B-1 cells, whose repertoire is selected by recognition of self antigen, belong to what may be earlier layer(s) and inherently maintain production of evolutionarily important antibody specificities that respond to pathogen-related, rather then antigen-specific signals.     

Buchbesprechungen

Psychotherapie Forum -     

Importance of culturing primary lymphocytes at physiological oxygen levels

Although studies with primary lymphocytes are almost always conducted in CO(2) incubators maintained at atmospheric oxygen levels (atmosO(2); 20%), the physiological oxygen levels (physO(2); 5%) that cells encounter in vivo are 2-4 times lower. We show here that culturing primary T cells at atmosO(2) significantly alters the intracellular redox state (decreases intracellular glutathione, increases oxidized intracellular glutathione), whereas culturing at physO(2) maintains the intracellular redox environment (intracellular glutathione/oxidized intracellular glutathione) close to its in vivo status. Furthermore, we show that CD3/CD28-induced T cell proliferation (based on proliferation index and cell yield) is higher at atmosO(2) than at physO(2). This apparently paradoxical finding, we suggest, may be explained by two additional findings with CD3/CD28-stimulated T cells: (i) the intracellular NO (iNO) levels are higher at physO(2) than at atmosO(2); and (ii) the peak expression of CD69 is significantly delayed and more sustained at physO(2) that at atmosO(2). Because high levels of intracellular NO and sustained CD69 tend to down-regulate T cell responses in vivo, the lower proliferative T cell responses at physO(2) likely reflect the in vitro operation of the natural in vivo regulatory mechanisms. Thus, we suggest caution in culturing primary lymphocytes at atmosO(2) because the requisite adaptation to nonphysiological oxygen levels may seriously skew T cell responses, particularly after several days in culture.     

Breast-conserving surgery for T3/T4 breast cancer: an analysis of 196 patients

Introduction Breast conservation therapy (BCT) increases quality of life and self-esteem of breast cancer patients. In special cancer centers up to 90% of patients are treated with BCT. T3/T4 breast cancer is one of the few contraindications for BCT. However, retrospective data suggest that BCT may be eligible in selected cases of T3/T4 breast cancer. Method We analyzed retrospectively 196 breast cancer patients (operated between 1995 and 2004) suffering from T3/T4 tumors and compared BCT and radiotherapy with mastectomy in these patients in terms of overall survival (OS), local recurrence free-survival (LRFS) and breast cancer-related death (BCRD). Result Demographic data showed no significant differences in prognostic factors between patients treated with mastectomy compared with BCT. Kaplan-Meier curves demonstrated no significant difference for OS, LRFS and BCRD between the two groups. Discussion Our data strongly suggest that BCT with R0 resection followed by radiotherapy is feasible in patients with T3/T4 breast cancer. Prospective studies have to be performed to further investigate this issue.     

Proxy screening tools improve the recognition of dementia in old-age homes: results of a validation study

BACKGROUND: Despite the high true prevalence of dementia, demential disorders of residents of old age homes may often be not recognized. There is a need for a standardised tool which includes observations of nursing staff. OBJECTIVE: To describe and validate the Dementia Screening Scale (DSS) for use by nursing staff in old-age homes. METHODS: All residents of 20 randomly selected old age homes in the city of Mannheim, Germany (n = 1, 922) were rated by nurses using the seven-item proxy dementia rating scale. Based on a subset of residents (n = 598) the DSS was validated against independent diagnostic assessments made by trained psychologists including the Mini-Mental-State-Examination (MMSE), the Dementia Scale of the Brief Assessment Schedule (BAS DEM), and the Washington University Clinical Dementia Rating (CDR). RESULTS: Using the CDR as a gold standard, the DSS correctly classified at a cut-off of 2/3, 85.8% of the mildly, moderately, or severely demented residents. The accuracy of the DSS was only a little worse than that of the MMSE and the BAS DEM. CONCLUSION: The DSS is well-suited for the recognition of dementia in old age homes. It achieved a better validity than global diagnosis-related staff assessments and compared to performance-based instruments. It is easier to apply, more economic, and associated with a fewer rate of non-response.     

Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of β-Amyloid in TH1 and TH17 Versions of Experimental Autoimmune Encephalomyelitis

β-Amyloid 42 (Aβ42) and β-amyloid 40 (Aβ40), major components of senile plaque deposits in Alzheimer's disease, are considered neurotoxic and proinflammatory. In multiple sclerosis, Aβ42 is up-regulated in brain lesions and damaged axons. We found, unexpectedly, that treatment with either Aβ42 or Aβ40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation. Aβ42 and Aβ40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive T helper 1 (T(H)1) or T(H)17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo Aβ42 and Aβ40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major proinflammatory cytokines and chemokines were reduced in the blood after Aβ peptide treatment. Protection conferred by Aβ treatment did not require its delivery to the brain: Adoptive transfer with lymphocytes from donors treated with Aβ42 attenuated EAE in wild-type recipient mice, and Aβ deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with Aβ treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of Aβ, there is exacerbated clinical EAE disease progression. Because Aβ42 and Aβ40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.