Effect of tyrphostins on programmed cell death in colon adenocarcinoma cell line LS-180.

Programmed cell death is an important process in the regulation of cellular proliferation, rest, differentiation and death. It is a genetically controlled process with characteristic biochemical and morphological features. Apoptosis directly regulates tumorigenesis and its induction could be a useful method of cancer therapy. Cancer cells could be influenced by some factors which induce apoptosis. We investigated the influence of tyrphostins, that specifically inhibits protein tyrosine kinases and stops the cell cycle in apoptosis of the colon adenocarcinoma cell line LS180. We used them at the concentration of 1-10 microM for 24 and 48 hours. We detected apoptosis using techniques that monitor either biochemical and morphological features of this process, such as staining with 7-amino-actinomycin D, staining with Grünwald-Giemsa, TUNEL reaction, in situ hybridization and with immunoperoxidase staining procedures. We examined the expression of genes and proteins connected with programmed cell death (p53, c-myc, p21, bcl-2). We estimated the results by cytophotometry and documented them by colour photography. We found that tyrphostin rapidly inhibits the cell cycle, particularly at the concentration of 5 microM. The expression of genes and proteins was strongly correlated with the increased apoptotic cell death conforming to the results of TUNEL and staining methods.

Weight-load marching as a method of conditioning Australian Army recruits.

This study compared weight-load marching to running in the conditioning of Australian Army recruits over an 11-week period. Mean improvements in VO2max were 11.9% and 8.9% in the run and walk groups, respectively. Both groups sustained significant attrition due to medical causes, with the ultimate dropout rate being 49% in both groups. Subjectively, the walk group was viewed as being better able to cope with military tasks than the run group, despite lower absolute and percentage improvements in VO2max. These results suggest that tests of aerobic capacity may not be appropriate in determining "military fitness."

Injuries in Australian Army recruits. Part I: Decreased incidence and severity of injury seen with reduced running distance.

Three hundred fifty male recruits were randomly allocated to either the standard recruit training program (N = 180) or substituted a weighted march activity for all running periods in the physical training program (N = 170). There were no other differences in the formal training program. The incidence of injury was 37.6 and 46.6% in the walk and run groups, respectively. The rate of injury was 52.9/100 recruits in the walk group and 61.7/100 in the run group. The exposure incidence was 12.8/1,000 hours of physical training in the walk group and 14.9/1,000 hours in the run group. There was no statistically significantly difference in the total number of injured recruits in the two groups (64 vs. 85, chi(2) = 2.90, p = 0.09, relative risk [RR] = 1.24). There were, however, significantly more lower-limb (43 vs. 75, chi(2) = 9.77, p = 0.0018, RR = 1.65) and knee injuries (15 vs. 35, chi(2) = 6.54, p = 0.011, RR = 2.14) in the Run group. Lower-limb injuries constituted 79.8% of all Run injuries and 61.1% of all Walk injuries. Injuries in the Run group produced more morbidity, with nearly double the number of days of restriction, hospitalization, and not fit for duty. Standardized morbidity rates showed an average of 5.4 days of restriction per injury in the Run group and 3.96 days of restriction per injury in the Walk group. Reduction of running distance in the physical training program resulted in significant reductions in both the incidence of lower-limb injury and the overall severity of injury.

Injuries in Australian Army recruits. Part II: Location and cause of injuries seen in recruits.

Three hundred fifty male recruits were randomly allocated to either the standard recruit training program (N = 180) or substituted a weighted-march activity for all formal run periods (N = 170) in the physical training program. All injuries were seen at a single medical facility, and the cause, location, and severity of injury were recorded in the medical documents. Lower-limb injuries constituted 79.8% of all Run injuries and 61.1% of all Walk injuries. Foot (18.9%), knee (16.7%), ankle (13.3%), and shoulder (8.9%) were the most common sites of injury in the Walk group. In the Run group, the most common sites were knee (32.1%), ankle (18.3%), foot (11.9%), and shin (7.3%). There were two stress fractures (tibial) in the Run group and none in the Walk group, giving the Run group an incidence of 1.1%. There were 10 medical discharges in the Walk group and 16 in the Run group. Ten (62.5%) of the Run and 2 (20%) of the Walk discharges were due to lower-limb causes. Of these, only 1 (10%) of the Walk and 4 (25%) of the Run injuries were not considered to be pre-existing conditions. Marching (30.0%), physical training (25.5%), and the obstacle course (11.1%) were the most frequent causes of injury in the Walk group. In the Run group, the leading causes were running (36.6%), physical training (19.2%), and the obstacle course (14.6%). Running was the major cause of knee injury in the Run group (17/35), whereas physical training was the major cause of knee injury in the Walk group (5/15). Running was also the major cause of other lower-limb injuries in the Run group (19/58), whereas marching was the major cause in the Walk group (19/50). Lower-limb injuries were more frequent in the Run group, with running cited as the major cause of these injuries.

Injuries in Australian Army recruits. Part III: The accuracy of a pretraining orthopedic screen in predicting ultimate injury outcome.

Three hundred fifty male recruits were divided into two groups: Walk (N = 170) and Run (N = 180). A physical screen was performed before the commencement of recruit training consisting of a visual assessment of the feet looking for pes planus, pes cavus, and deformities of the toes. Each recruit was also asked if he had sustained any injury in the preceding 2 years. The visual findings and history of prior injury were noted and compared with actual injuries sustained during the 12-week training course. Fifty-three subjects in the Walk group and 54 in the Run group were identified as being at risk as a consequence of the screen. The sensitivity of the screen for predicting the subsequent injury was 34.4% in the Walk group and 31.8% in the Run group. The specificity was 72.6 and 77.4% in the Walk and Run groups, respectively. The predictive value of the test was 44.9% in the Walk group and 50.9% in the Run group. When reinjury was examined, the sensitivities fell to 9.4% (Walk) and 4.7% (Run) and the specificities to 57.5% (Walk) and 50.5% (Run). The screen correctly identified only 1 of 10 medical discharges in the Walk group and 2 of 16 in the Run group. The screening examination had poor sensitivity, specificity, and predictive value, and more than half of those thought to be at risk did not subsequently sustain an injury. Anecdotal beliefs that improvements in medical screening would reduce recruit wastage were not borne out. Abnormalities of the foot (pes planus, pes cavus, hallux valgus) were not significant factors in the development of injury during recruit training.

The effect of a modified physical training program in reducing injury and medical discharge rates in Australian Army recruits.

This uncontrolled observational study examined the injury and medical discharge outcomes in 318 female and 1,634 male recruits as a result of changes to the Australian Army recruit physical training program. Changes included cessation of road runs, introduction of 400- to 800-m interval training, reduction in test run distance from 5 to 2.4 km, standardization of route marches, and the introduction of deep-water running. There was a 46.6% reduction in the rate of total injury presentation (chi 2 = 14.31, p = 0.0002) after the change. The annual rate of male medical discharges decreased 40.8% from 81.1/1,000 recruits in 1994/1995 to 47.0/1,000 recruits in 1995/1996 (chi 2 = 26.33, p = 0.0001). Female rates increased 58.3% from 104/1,000 recruits to 164.2/1,000 recruits (chi 2 = 6.09, p = 0.014). The decrease in the male medical discharge rate resulted in an estimated saving of $1,267,805 Australian. Bone scans were reduced by 50%, resulting in an estimated annual saving of $61,539 Australian. The disparity between male and female injury rates is a concern. The merits of mixed-gender physical training should be reviewed in the light of these observations, and the establishment of initial entry fitness standards for recruit training may need to be considered.

Organ retrieval in donors suspected of cancer: single-center experience.

BACKGROUND: The transmission of cancerous cells with a transplanted organ is among the most serious complications of transplant surgery. Detailed preoperative tests seek to reduce the risk of transmission of viral and bacterial infections as well as to prevent donor-derived malignancy following organ transplantation. The objective of this study was to report our experience among cadaveric donors who we suspected of cancer. MATERIALS AND METHODS: We performed a retrospective search of the medical records of 75 potential cadaveric donors referred to our unit between January 2007 and December 2010. Our focus, however, was on donors suspected of cancer. RESULTS: Among 75 potential cadaveric donors 22 (29%) revealed features suggestive of cancer: physical signs of tumor pre- or intraoperatively: elevation of serum levels of a cancer marker; or an abnormal finding on radiological imaging. Among the latter group, 15 donors necessitated urgent histopathologic examination to rule out or confirm cancer. In four cases, organ transplantation was abandoned following the examination, including three cases in which a tissue diagnosis of cancer was evident and in one case, the examination was inconclusive to exclude cancer. In the remaining 14 cases, the histopathologic examination did not reveal cancer; thus transplantation was performed. CONCLUSIONS: Thorough histopathologic examination is essential in all potential donors who are suspected of cancer to prevent donor-derived malignancy following transplantation. In some cases, however, the tissue sampling is not conclusive; hence, transplantation must be abandoned. Even the most precise examination of the donor does not protect the recipient from the risk of transmission of cancer.

Successful kidney transplantation in a patient with multiple endocrine neoplasia type 2A syndrome: case study.

We present the case of a 37-year-old patient diagnosed with multiple endocrine neoplasia type 2A (MEN 2A) syndrome, as confirmed by genetic tests, who underwent the transplantation of a kidney from a cadaveric donor. MEN 2A, a hereditary autosomal dominant syndrome, is caused by the mutation of the RET proto-oncogene. In almost all patients this syndrome, is characterized by the occurrence of medullary thyroid cancer and pheochromocytoma; in some individuals also hyperparathyroidism. The available literature has not documented a kidney transplantation performed in Poland for this indication.

Gastrointestinal blood loss in triathletes: it's etiology and relationship to sports anaemia.

Twenty male triathletes (R 18-39 mean = 27.5 yrs) provided blood and faecal samples during intense training, pre-race taper and post-competition. All answered a closed-end questionnaire on intake of aspirin, NSAIDS, Vitamin C, iron and red meat. History of GIT blood loss and training distances were also obtained. Blood samples were taken on three occasions and analysed for Haemoglobin(Hb) and Serum Ferritin concentrations. Faecal specimens were collected on five occasions and assessed for blood loss using Haemoccult II and Monohaem (a monoclonal antibody test specific for human haemoglobin). Mean Hb and 95% confidence intervals at the three stages were 14.53gm/l (13.95-15.10), 14.9gm/l (14.46-15.34), 14.57gm/l (14.18-14.97) respectively. There was a small, but statistically significant, increase in Hb during the pre-race taper period (paired t = 2.65, p < 0.05), and a non-significant drop in Hb post-event (paired t = 1.89, p = 0.075). Mean ferritin, MCV and haematocrit values did not significantly change. Eighty percent of the group exhibited faecal blood loss on one or more of the tests used. There were significant increases in both Haemoccult (chi 2 = 5.44, p < 0.04) and Monohaem (chi 2 = 7.36 p < 0.02). Regression analysis demonstrated a significant relationship between training Hb and total training intensity (R = -0.61, F1,l5 = 8.98, p < 0.009) and training run intensity (R = -0.55, F1,l5 = 6.17, p < 0.026), as estimated using Coopers aerobic points system. These results confirm that GIT blood loss is common in endurance athletes, and appears to be related to exercise intensity. The possible mechanisms of blood loss are discussed.

Rb1 gene expression in B-cell lymphocytic leukaemia cases with deletion in the 13q14 region.

Recent studies have been carried out to delineate further the role of the Rb1 gene in B-cell chronic lymphocytic leukaemia (B-CLL). The suggested role of the Rb1 gene in this disease was based on cytogenetic data. CLL patients (40 in toto) were examined using cytogenetic and molecular biological methods. R-banding analysis of metaphase chromosomes revealed aberrations in only seven cases containing either the Rb1 gene or a chromosome 13 monosomy. No evident differences were found by RT-PCR analysis of Rb1 gene expression. The amounts of the RT-PCR products obtained appeared to be approximately equal in all cases, and was independent of the clinical stage, immunophenotypes and LPS or TPA stimulation.