Apoptosis and inflammation

During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972) introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases

Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide

Immunoreactive endothelin (ETi) and atrial natriuretic peptide (ANPi) blood levels were measured by radioimmunoassay in patients with clinically defined sepsis. The interaction between these two peptides and their relation to circulatory shock and mortality were studied. All septic patients (n = 16) had significantly higher ETi (22.3 ± 11.1 pg/ml) and ANPi (398.3 ± 154.3 pg/ml) plasma concentrations compared to control subjects (ETi, 4.1 ± 1.2; ANPi, 59.1 ± 14.8 pg/ml; n = 13). ETi levels followed the severity of illness according to the APACHE II scoring system and were higher in patients who did not survive. ETi levels were significantly higher in the presence of shock and bacteraemia. Furthermore, ETi correlated well with plasma lactate (r = 0.83, p < 0.05), but not with renal function. ANPi levels did not show correlation with any of these determinants. Serial blood sampling, six consecutive days after admission, showed that ETi levels gradually decreased in normotensive patients in contrast to patients with septic shock. ANPi levels did not show systematic changes in time, and no relationship was observed between ETi and ANPi levels. These results suggest that plasma ETi levels are indicative for disease severity and might have prognostic significance. The role of ANPi during sepsis remains to be eludicated

Selective Expansion of Cross-Reactive Cd8+ Memory T Cells by Viral Variants

The role of memory T cells during the immune response against random antigenic variants has not been resolved. Here, we show by simultaneous staining with two tetrameric major histocompatibility complex (MHC)–peptide molecules, that the polyclonal CD8+ T cell response against a series of natural variants of the influenza A nucleoprotein epitope is completely dominated by infrequent cross-reactive T cells that expand from an original memory population. Based on both biochemical and functional criteria, these cross-reactive cytotoxic T cells productively recognize both the parental and the mutant epitope in vitro and in vivo. These results provide direct evidence that the repertoire of antigen-specific T cells used during an infection critically depends on prior antigen encounters, and indicate that polyclonal memory T cell populations can provide protection against a range of antigenic variants

Apoptotic cell death, detected ex vivo in peripheral blood lymphocytes of HIV-1 infected persons

In HIV-1 infection the ongoing depletion of CD4+ T-lymphocytes is believed, to a large extent, to be due to apoptosis. Until now quantitative information about in vivo apoptosis of lymphocytes in HIV-patients is scarce because of the very nature of the apoptotic process. Successful detection of apoptosis ex vivo requires the recognition of the initial phase of this process, because at a later stage the cells may not remain any longer in the circulation. We measured quantitatively the amount of early apoptotic peripheral blood lymphocytes directly ex vivo in HIV-1 infected patients using a recently described flow cytometric assay. With this method we observed in an unselected heterogenous group of twelve HIV-infected individuals a median percentage of apoptotic lymphocytes to be significantly higher than in ten healthy controls. To the best of our knowledge this is the first report of ex vivo observed increased apoptosis of peripheral blood lymphocytes in HIV-infected persons

A long-lasting, complete hematologic and cytogenetic remission of chronic myelogenous leukemia after treatment with busulfan alone

A 44-year-old man suffering from cytogenetically and molecularly proven Philadelphia translocation-positive chronic myelogenous leukemia in chronic phase was treated with busulfan for 18 months and studied during a follow-up period of 13 years. Hematologically and cytogenetically, he attained a continuing complete remission, although at one point (9.5 years) at least, after attaining complete remission molecular analysis indicated the presence of minimal residual disease

Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus.

We established an international consortium to review and discuss relevant clinical evidence in order to develop expert consensus statements related to cancer management during the severe acute respiratory syndrome coronavirus 2-related disease (COVID-19) pandemic. The steering committee prepared 10 working packages addressing significant clinical questions from diagnosis to surgery. During a virtual consensus meeting of 62 global experts and one patient advocate, led by the European Society for Medical Oncology, statements were discussed, amended and voted upon. When consensus could not be reached, the panel revised statements until a consensus was reached. Overall, the expert panel agreed on 28 consensus statements that can be used to overcome many of the clinical and technical areas of uncertainty ranging from diagnosis to therapeutic planning and treatment during the COVID-19 pandemic

Hypnosis as a treatment of chronic widespread pain in general practice: A randomized controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>Hypnosis treatment in general practice is a rather new concept. This pilot study was performed to evaluate the effect of a standardized hypnosis treatment used in general practice for patients with chronic widespread pain (CWP).</p> <p>Methods</p> <p>The study was designed as a randomized control group-controlled study. Sixteen patients were randomized into a treatment group or a control group, each constituting eight patients. Seven patients in the treatment group completed the schedule. After the control period, five of the patients in the control group also received treatment, making a total of 12 patients having completed the treatment sessions. The intervention group went through a standardized hypnosis treatment with ten consecutive therapeutic sessions once a week, each lasting for about 30 minutes, focusing on ego-strengthening, relaxation, releasing muscular tension and increasing self-efficacy. A questionnaire was developed in order to calibrate the symptoms before and after the 10 weeks period, and the results were interpolated into a scale from 0 to 100, increasing numbers representing increasing suffering. Data were analyzed by means of T-tests.</p> <p>Results</p> <p>The treatment group improved from their symptoms, (change from 62.5 to 55.4), while the control group deteriorated, (change from 37.2 to 45.1), (p = 0,045). The 12 patients who completed the treatment showed a mean improvement from 51.5 to 41.6. (p = 0,046). One year later the corresponding result was 41.3, indicating a persisting improvement.</p> <p>Conclusion</p> <p>The study indicates that hypnosis treatment may have a positive effect on pain and quality of life for patients with chronic muscular pain. Considering the limited number of patients, more studies should be conducted to confirm the results.</p> <p>Trial Registration</p> <p>The study was registered in ClinicalTrials.gov and released 27.08.07 Reg nr NCT00521807 Approval Number: 05032001.</p