Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.     

Predictive power of various models for longitudinal attachment level change

Abstract Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naive mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.     

Provider attitudes regarding use of an immunization information system to identify children with asthma for influenza vaccination.

OBJECTIVES: Despite longstanding national guidelines, many children with asthma do not receive annual influenza vaccinations. Information from Medicaid-administrative claims data was integrated into the Michigan Care Improvement Registry (MCIR) to prompt providers regarding influenza vaccination among children with high-risk conditions such as asthma. The attitudes of pediatric primary care providers regarding the implementation of this system were assessed. METHODS: A survey was sent in February 2006 to office-based general pediatricians (n = 300) and family physicians (n = 300) in Michigan. The survey focused on influenza vaccination during the 2005-2006 influenza season and attitudes regarding a reminder system for providers using the MCIR. RESULTS: Overall response rate was 67 percent. MCIR participation was high (91%) among respondents, and most (83%) had MCIR information available to them prior to visits with pediatric patients. Most physicians (75%) considered the MCIR high-risk indicator for influenza vaccination a feature that they would find helpful. Some respondents reported concerns that the reminder system is limited to Medicaid patients only (44%) and regarding the completeness of Medicaid data to identify children with asthma (24%). CONCLUSIONS: Physicians have a positive overall view of a statewide registry-based automated reminder system to assist in identifying children with asthma for influenza vaccination, albeit with specific areas of concern.     

Physical fitness and all-cause mortality. A prospective study of healthy men and women

We studied physical fitness and risk of all-cause and cause-specific mortality in 10,224 men and 3120 women who were given a preventive medical examination. Physical fitness was measured by a maximal treadmill exercise test. Average follow-up was slightly more than 8 years, for a total of 110,482 person-years of observation. There were 240 deaths in men and 43 deaths in women. Age-adjusted all-cause mortality rates declined across physical fitness quintiles from 64.0 per 10,000 person-years in the least-fit men to 18.6 per 10,000 person-years in the most-fit men (slope, -4.5). Corresponding values for women were 39.5 per 10,000 person-years to 8.5 per 10,000 person-years (slope, -5.5). These trends remained after statistical adjustment for age, smoking habit, cholesterol level, systolic blood pressure, fasting blood glucose level, parental history of coronary heart disease, and follow-up interval. Lower mortality rates in higher fitness categories also were seen for cardiovascular disease and cancer of combined sites. Attributable risk estimates for all-cause mortality indicated that low physical fitness was an important risk factor in both men and women. Higher levels of physical fitness appear to delay all-cause mortality primarily due to lowered rates of cardiovascular disease and cancer.     

Social and reproductive characteristics of the first 100 couples treated by in vitro fertilisation programme at National Women's Hospital, Auckland

Reproductive and social histories of the first 100 patients attending the in vitro fertilisation (IVF) programme at National Women's Hospital, Auckland, have been studied. The average age at first treatment was 31.6 (SD 3.9) for women, and 34.2 (4.6) for men. The couples had been married 7.6 (3.3) years and had experienced 6.7 (3.2) years infertility. It was a second marriage for 16. The husbands had on average a higher social classing than the population (class: number [population]--1:16 (7%), 2:18 (14%), 3:42 (28%), 4:19 (29%), 5:4 (14%), 6:1 (8%); but this bias diminished in the next 159 couples. Nine couples withdrew before their quota of cycles, 7 from stress. Tubal disease was the cause of infertility in 93, but in 69 its origin was untraceable. In 22 it could be attributed to pelvic inflammatory disease (eight associated with IUCDs and 2 with sexually transmitted disease) and in two to sterilisation. Although 59 women had a history of having conceived, only 34 were parous, and only 11 had a child of the current union.     

Physiologic responses to heavy-resistance exercise with very short rest periods

Heavy-resistance exercise utilizing very short rest periods is commonly used by body builders to prepare for competition. The purpose of this study was to compare the acute responses of this type of heavy-resistance exercise protocol in competitive body builders (BB) and power lifters (PL). Nine male BB and eight PL were matched for age, size and experience. A ten-station heavy-resistance exercise protocol was used. Each subject performed three sets of 10 repetition maximum (RM) with 10-s rest between sets and alternated 30-s and 60-s rest periods between exercises. No differences were observed in total work between the groups, but BB used a significantly (P less than 0.05) higher percentage of their 1 RM in the bench press and leg press exercises. Heart rate, ratings of perceived exertion (RPE), and lactate levels were obtained during the exercise protocol; significant (P less than 0.05) increases were observed above rest for these variables. RPE was significantly correlated with lactate levels (r = 0.84). Plasma epinephrine, norepinephrine, dopamine, cortisol, and lactate levels significantly increased from pre- to 5 min post-exercise. Mean plasma volumes were reduced -16.6 (+/- 3.64)% and -20.6 (+/- 8.32)% following the exercise protocol for BB and PL, respectively. Significant (P less than 0.05) decreases in eosinophil counts were observed following exercise. No significant differences were observed between BB and PL for any of the physiologic responses measured. PL exhibited a higher incidence (100%) of clinical symptoms of dizziness and nausea compared to BB (11.1%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Single photon emission computed tomography using 99mTc-HM-PAO in the routine evaluation of Alzheimer's disease

Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.