Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy.

BACKGROUND: Lymphoma patients undergoing therapy must cope with the side-effects of the disease itself, therapy and associated immobility. Peripheral neuropathy (PNP), loss of balance control and weakness not only diminishes patients' quality of life (QOL), it can also affect planning and the dosage of therapy. Exercise may enable patients to reverse these declines, improving their performance level and QOL. PATIENTS AND METHODS: We carried out a randomized, controlled trial, assigning 61 lymphoma patients either to a control group (CG; N=31) or to a 36-week intervention (IG; N=30), consisting of sensorimotor-, endurance- and strength training twice a week. Primary end point was QOL; secondary end points included movement coordination, endurance, strength and therapy-induced side-effects. RESULTS: Intergroup comparison revealed improved QOL- (ΔT1-T0; P=0.03) and PNP-related deep sensitivity in the IG: 87.5% were able to reduce the symptom, compared with 0% in the CG (P<0.001). Significant differences in the change of balance control could be found between the groups, with the IG improving while the CG steadily declined (monopedal static ΔT3-T0; P=0.03; dynamic ΔT3-T0; P=0.007; perturbed mono-ΔT3-T0; P=0.009 and bipedal ΔT3-T0; P=0.006), failed attempts (monopedal static ΔT3-T0; P=0.02, dynamic ΔT3-T0; P<0.001and perturbed ΔT3-T0; P=0.006) and improved time to regain balance (ΔT3-T0; P=0.04). Moreover, the change in the aerobic performance level (ΔT3-T0; P=0.05) and additional amount of exercise carried out per week [metabolic equivalent (MET); P=0.02] differed significantly across groups. CONCLUSIONS: Exercise, especially sensorimotor training, is a feasible and promising method to support cancer patients during therapy. It improves patients QOL, reduces restrictions from side-effects such as PNP and improves patients' balance control, physical performance level and mobility. GERMAN CLINICAL TRIALS REGISTER NUMBER: DRKS00003894.

[Do smoking hospital inpatients get therapies for cessation? Experiences of health care professionals]. / Bekommen rauchende Patienten in der Klinik Angebote zur Entwöhnung? Erfahrungen von Mitarbeitern.

AIMS: To conduct a preliminary study into the attitudes and current practices of health professionals towards providing tobacco dependence treatment to hospitalized patients. METHODS: A staff survey was distributed within four hospital departments at the University Medical Center Freiburg. Surveys were received from 92 respondents (response rate 28.3%, of them 65.2% nurses and 27.3% doctors). RESULTS: Most of respondents reported that they 'often' or 'always' ask patients whether they smoke and advise patients to quit, but only 27.5% encourage patients to set a quit date or informed them about medication (21.7%). Few health professionals (14.1%) believed that they were adequately trained to provide tobacco dependence treatment, and knowledge of guidelines for treatment was minimal. Lack of time was cited as a barrier by half of respondents. DISCUSSION: The results of this small study of health professionals reveal a high level of recognition of the importance of providing tobacco dependence treatment, but that they do not routinely assist patients. Insufficient training was mentioned as the major barrier to provide more effective assistance and should be acknowledged in regular trainings.

Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets.

Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.

Anaemia and cigarette smoking.

Cigarette smoking causes numerous diseases that are associated with anaemia but the resulting low haemoglobin levels may be counterbalanced by increased red blood cell production caused by chronic exposure to carbon monoxide from cigarette smoke. Diverse mechanisms are involved in influencing the development or the course of anaemic disease in smokers. This article presents an evaluation of the current literature on the impact of cigarette smoking on various forms of anaemia.

[Arterial ocular occlusion associated with systemic venous thrombophilia--2 case reports]. / Arterielle okuläre Gefässverschlüsse bei systemischer venöser Thrombophilie--2 Kasuistiken.

BACKGROUND: Arterial ocular occlusions in apparently healthy young men are unusual. Because of inconsistent study results there is a great amount of insecurity with respect to the reasonable diagnostic approach in such a scenario. We report on the process of diagnostic steps in two young men with arterial ocular occlusion such as non-arteritic optic neuropathy (NAION) and branch retinal arterial occlusion (BRAO). CASE REPORT: Here, we report on two hitherto healthy young men who suffered from ocular arterial occlusions. Because of the apparent arterial perfusion deficit at first thrombocyte aggregation-inhibiting substances were recommended. On searching for the underlying embolic source in both men a significant arterial-venous cardiac and pulmonary shunt volume was identified. Additional screening for risk factors for venous thrombosis resulted in the identification of Factor V Leiden as well as hyperhomocysteinemia. CONCLUSION: These two cases stress the importance to exclude possible arterial-venous shunts and, if identified, the need to search for additional risk factors for venous thrombosis in patients with arterial embolic ocular disease.

The cationic region from HIV tat enhances the cell-surface expression of epitope/MHC class I complexes.

The potential of genetic immunization has been acknowledged for almost a decade, but disappointing immunogenicity in humans has delayed its introduction into the clinical arena. To try to increase the potency of genetic immunization, we and others have evaluated 'translocatory' proteins, which are thought to exit living cells by an uncharacterized pathway, and enter neighboring cells in an energy-independent manner. Several laboratories, including our own, have begun to question these remarkable properties. Our previous studies showed that the ability of an epitope to induce major histocompatibility complex (MHC) class I restricted CD8(+) T cells was, indeed, enhanced by its being attached to the proposed translocatory sequence of the HIV-1 tat protein. However, we found little evidence that the increased immunogenicity resulted from transfer of the fusion peptide between living cells, and we proposed that it resulted instead from an increased epitope/MHC expression on the surface of transfected cells. Here, we directly test this hypothesis. We show that cells cotransfected with plasmids encoding an epitope, and the relevant MHC class I allele, can stimulate epitope-specific T cells, and that attachment of the epitope to a putative translocatory sequence - which we term herein an 'integral cationic region' (ICR) - leads to a marked increase in stimulatory activity. This elevated stimulatory capacity does not result from a nonspecific increase in MHC class I expression. We use a high-affinity T-cell receptor (TcR) specific for the epitope/MHC combination to quantitate directly the cell-surface expression of the immunogenic complex, and we show that the attachment of the tat ICR to an epitope results in a substantial enhancement of its cell-surface presentation. These data suggest an alternative explanation for the immune enhancement seen with ICRs.

Full-length proteins attached to the HIV tat protein transduction domain are neither transduced between cells, nor exhibit enhanced immunogenicity.

Several proteins have been accorded the unusual ability to translocate across cell membranes in a receptor-independent and temperature-independent manner, and this activity has been mapped to a highly basic series of residues currently termed a 'protein transduction domain' (PTD). This translocatory attribute, if authentic, would be valuable for purposes of gene therapy and vaccination. We have evaluated the PTD from the human immunodeficiency virus type 1 (HIV) tat protein and we conclude that, when synthesized de novo, (1) the HIV tat PTD does not enhance the immunogenicity of a full-length protein to which it is tethered; and (2) the HIV tat PTD does not cause intercellular transfer of an attached marker protein, as judged by careful quantitative analyses. From our data, and from a review of published materials, we suggest that contrary to current dogma there is little evidence that these supposedly translocatory proteins can move between live cells. Furthermore, we suggest that PTDs do not act to enhance translocation, but instead merely to increase binding to the cell surface; in which case, the term 'protein transduction domain', and the related acronym, are misnomers which should be abandoned. Our conclusions explain why the most dramatic demonstrations of PTD efficacy have been obtained using fixed cells and/or denatured proteins, and have obvious implications for gene therapy and vaccination.

Enhancing T cell activation and antiviral protection by introducing the HIV-1 protein transduction domain into a DNA vaccine.

Protein transduction domains (PTD), which can transport proteins or peptides across biological membranes, have been identified in several proteins of viral, invertebrate, and vertebrate origin. Here, we evaluate the immunological and biological consequences of including PTD in synthetic peptides and in DNA vaccines that contain CD8(+) T cell epitopes from lymphocytic choriomeningitis virus (LCMV). Synthetic PTD-peptides did not induce detectable CD8(+) T cell responses. However, fusion of an open reading frame encoding a PTD to an epitope minigene caused transfected tissue culture cells to stimulate epitope-specific T cells much more effectively. Kinetic studies indicated that the epitope reached the surface of transfected cells more rapidly and that the number of transfected cells needed to stimulate T cell responses was reduced by 35- to 50-fold when compared to cells transfected with a standard minigene plasmid. The mechanism underlying the effect of PTD linkage is not clear, but transit of the PTD-attached epitope from transfected cells to nontransfected cells (cross presentation) seemed to play, at most, a minimal role. Mice immunized once with the plasmid encoding the PTD-linked epitope showed a markedly accelerated CD8(+) T cell response and, unlike mice immunized with a standard plasmid, were completely protected against a normally lethal LCMV challenge administered only 8 days post-immunization.