Periodic loss of reactivity of a myeloma tumor with cytotoxic thymus-derived lymphocytes.

During each transplantation passage of a line of mouse myeloma tumor MOPC-315 through syngeneic (BALB/c) hosts, the tumor cells lose reactivity with cytotoxic thymus-derived lymphocytes directed against products of the BALB/c major histocompatibility complex (H-2d) and regain reactivity on transfer to fresh hosts. In contrast to this cyclical change, the tumor cells remain uniformly reactive with anti-H-2d alloantisera throughout the transplantation cycle.     

Changing patterns of therapeutic agents in the elderly: a ten-year overview.

Drug use patterns in a large ambulatory elderly population were studied cross-sectionally over a 10-year period. There were 24192 drug histories obtained on 4509 individuals during the period from 1 August 1978 to 31 July 1988. The average number of drugs used per person increased from 3.22 in 1978-9 to 3.94 in 1987-8. Prescribed drug use increased by 0.52 per person compared with an increase of 0.21 for nonprescribed medication. Analysis of two mutually exclusive groups of participants from 1978-9 and 1987-8 revealed a significant (p less than 0.0001) increase in the use of nonprescribed medication but no significant increase in the use of prescribed medication after adjusting for age and sex effects. The four most frequently used therapeutic classes of drugs in 1978-9 as a percentage of all drugs used were antihypertensives (10.8%), analgesic-antipyretics (6.4%), antirheumatic (6.4%), and cathartics (5.4%) compared with the antihypertensives (9.5%), analgesic-antipyretics (5.9%), anticoagulants (5.5%), and antirheumatic (4.6%) for the 1987-8 period.     

Capsaicin-Induced Cardioprotection. Is Hypothermia or the Salvage Kinase Pathway Involved?

Purpose

Topical capsaicin application was shown to reduce infarct size in experimental animal models. We hypothesized that cardioprotective properties of topical capsaicin application could be related to its hypothermic effect.

Methods

In the first arm of the study, anesthetized rats received capsaicin cream (Caps group) or vehicle (Control group, Ctrl) applied either 15 or 30 min prior to a 30-min coronary artery occlusion followed by 2-h reperfusion. Core body temperature was allowed to run its course, and was monitored via rectal probe. At the end of the protocol, hearts were excised and risk zone and infarct size were measured. In an additional set of animals, hearts were excised immediately after a 15-min application of capsaicin/vehicle, and were used to measure phosphorylated Akt and Erk1/2 with western blots. In the second arm of the study Ctrl (n?=?6) and Caps-treated (n?=?5) animals were subjected to the same protocol as rats in the first arm, but core body temperature was maintained at 36 °C.

Results

In the first arm of the study, capsaicin produced a rapid decrease in rectal temperature ranging from 0.22 to 1.78 °C at pre-occlusion, with a median level of 0.97 °C. A capsaicin-induced temperature decrease of >0.97 °C was associated with a 31.2 % smaller infarct compared to the control group. Capsaicin treatment induced an increase in the levels of phosphorylated Akt and Erk1/2 at the end of capsaicin cream application. No increase in the phosphorylation of downstream p70S6 was observed. Levels of phosphorylated Akt- and Erk1/2 did not correlate with temperature changes after treatment. In the second arm of the study, in which body core temperature was maintained at 36 °C, no change in the infarct size was observed in the capsaicin vs. control group.

Conclusion

In the current study we for the first time demonstrated that the capsaicin induced cardioprotective effect might be related to mild hypothermia, caused by capsaicin topical application. The salvage kinase pathway appears not to be critical for capsaicin-induced cardioprotection.     

The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol

Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin–Frankfurt–Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan–Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20?×?10⁹/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.     

Asymmetrical movements of the lumbopelvic region: Is this a potential mechanism for low back pain in people with lower limb amputation?

Low back pain (LBP) is a major secondary disabling condition following lower limb amputation including persons with above-knee and below-knee amputation. Whilst the increasing prevalence of this musculoskeletal problem in people with lower limb amputation is well recognised, the mechanisms of LBP in this population have been poorly explored. Asymmetrical movements and loading patterns have been found in persons following lower limb amputation and linked to the high prevalence of LBP in this population. However, some argue that such asymmetries are part of the ‘normal’ adaptive process following lower limb amputation. We hypothesise that there is potential for some of the kinematic and kinetic adaptations in the lumbopelvic and trunk region to be ‘mal-adaptive’, potentially acting as a contributing factor for the onset or maintenance of LBP symptoms in this population. Evidence for movement and muscle asymmetries around the lumbopelvic and lower limb region provides some support for an association between LBP and movement asymmetry in the general population. It is therefore reasonable to hypothesise that movement asymmetries will demonstrate an association with LBP in lower limb amputee populations. Previous studies investigating movement and loading patterns within this population have focused mainly on gait analysis. Therefore, there is a need for further research to investigate the presence and potential association of asymmetrical movement patterns of the lumbopelvic region with LBP in a range of specific functional tasks. Results of such studies will identify the asymmetrical movement patterns and functional tasks associated with LBP in this population. Furthermore, it will inform future case-control and longitudinal studies to specifically investigate the putative links for such asymmetrical movement patterns as risk factors to LBP in this population.