Effect of physical training on treadmill exercise capacity, collateral circulation and progression of coronary disease

The increased exercise capacity after physical training in patients with coronary artery disease has been attributed to improved oxygen supply to the myocardium by way of increased collateral circulation or reduction of myocardial oxygen consumption by extracardiac factors, or both. Fourteen patients aged 43 to 61 years (mean 51 years) with 50 percent or greater obstruction in one, two or three vessels (three, six and five patients, respectively) underwent 13 months of physical training. Clinical status was either stable or improved with training. Treadmill exercise capacity, as measured by oxygen consumption, increased 25 percent from 21.9 ± 4.8 (standard deviation) to 27.4 ± 4.1 ml/kg-min at heart rates of 154 ± 17 and 156 ± 12 beats/min, respectively. After training, new collateral vessels, apparently secondary to progression of the disease, were observed in 2 of 21 arteries significantly but not completely obstructed before training. These data are in contrast to those reported for trained dogs with incomplete obstruction. Coronary arterial lesions progressed in only 4 of 14 patients. Coronary arteriographic data from this laboratory do not support the hypothesis that the increased exercise capacity after training in patients with coronary disease can be attributed to the development of collateral circulation. It is possible that physical training may retard the progression of coronary artery disease.     

Transient Intraventricular Conduction Delay Associated with Concurrent Intake of Propafenone and Antineoplastic Agents

An 82-year old man was admitted with acute pulmonary edema. Myocardial ischemia and electrolyte abnormalities were excluded and he responded promptly to frusemide, nitrates and morphine. On admission, the duration of the QRS interval was markedly abnormal at 240 ms with a nonspecific intraventricular conduction defect pattern, of left bundle branch block type. This finding was not present three weeks prior to his admission, and was felt to be the result of drug interaction between propafenone and antineoplastic agents, as evidenced by resolution of the clinical and electrocardiographic picture after discontinuation of these agents.     

Functional viability profiles of breast cancer

The design of targeted therapeutic strategies for cancer has largely been driven by the identification of tumor-specific genetic changes. However, the large number of genetic alterations present in tumor cells means that it is difficult to discriminate between genes that are critical for maintaining the disease state and those that are merely coincidental. Even when critical genes can be identified, directly targeting these is often challenging, meaning that alternative strategies such as exploiting synthetic lethality may be beneficial. To address these issues, we have carried out a functional genetic screen in >30 commonly used models of breast cancer to identify genes critical to the growth of specific breast cancer subtypes. In particular, we describe potential new therapeutic targets for PTEN-mutated cancers and for estrogen receptor-positive breast cancers. We also show that large-scale functional profiling allows the classification of breast cancers into subgroups distinct from established subtypes. SIGNIFICANCE: Despite the wealth of molecular profiling data that describe breast tumors and breast tumor cell models, our understanding of the fundamental genetic dependencies in this disease is relatively poor. Using high-throughput RNA interference screening of a series of pharmacologically tractable genes, we have generated comprehensive functional viability profiles for a wide panel of commonly used breast tumor cell models. Analysis of these profiles identifies a series of novel genetic dependencies, including that of PTEN-null breast tumor cells upon mitotic checkpoint kinases, and provides a framework upon which additional dependencies and candidate therapeutic targets may be identified.     

Metabolic syndrome prevalence and characteristics in Greek adults with familial combined hyperlipidemia

Familial combined hyperlipidemia (FCH) is closely related with metabolic syndrome (MetSyn), and coronary artery disease (CAD) is positively associated to MetSyn and FCH. In this study, we evaluated the prevalence of MetSyn and its components between patients with FCH and a control group. We also investigated the role of MetSyn and diabetes mellitus (DM) on the incidence of CAD within the FCH group. Our study population consisted of 463 male and 243 female patients with FCH who were not receiving any hypolipidemic treatment, and 1128 men and 1154 women who came from the same geographical region. The prevalence of MetSyn was 42% and 19.8% among FCH subjects and controls, respectively, whereas MetSyn increased with age in both groups. The prevalence of CAD was 15.3% in the FCH group. Moreover, after dividing FCH patients into 3 subgroups, with and without MetSyn and with DM, CAD prevailed at a percentage of 15.2%, 11.1%, and 26.5%, respectively. However, statistically significant differences in the prevalence of CAD were observed only between FCH subjects with DM compared with the other 2 subgroups, even when an adjustment for age, sex, and smoking was conducted. People with FCH and MetSyn differed in several anthropometric, biochemical, and clinical characteristics, compared with the non-MetSyn subgroup of FCH. MetSyn is more prevalent in the FCH than in the control group. Among subjects with FCH, only DM was significantly associated with an increase in the prevalence of CAD in this subgroup compared with FCH individuals with or without MetSyn.     

Screening for preparatory grief in advanced cancer patients

The present study aims to determine the use of Preparatory Grief in Advanced Cancer Patients (PGAC) Scale for screening preparatory grief according to independent criterion standards (ie, the Hospital Anxiety and Depression [HAD] Total scale and the HAD Depression and Anxiety subscales) and to establish an optimal cutoff point for discriminating between subjects with and without preparatory grief. One hundred advanced cancer patients treated in a Pain Relief and Palliative Care Unit completed the PGAC and HAD Scales, while researchers recorded data on demographic characteristics, disease status, and treatment regimen. Optimal balance between sensitivity and specificity for the PGAC Scale as a screening instrument was achieved at a cutoff score of 40+ for all the criterion standards (ie, HAD Total, HAD Anxiety, and HAD Depression), giving a sensitivity range between 84% and 92%, and specificity between 70% and 86%. The area under the receiver operating characteristic curve ranged between 0.867 and 0.968. The PGAC Scale had a favorable sensitivity and specificity in identifying cases of preparatory grief. The receiver operating characteristic analyses demonstrated that the scale is a useful screening instrument in advanced cancer patients.     

Support for smoke-free policies in a pro-smoking culture: findings from the European survey on tobacco control attitudes and knowledge

Objectives  

To assess support for tobacco control policies between smokers and non-smokers, and the effects of nicotine dependence on smokers’ policy support in a country with high smoking rates and pro-smoking norms.     

Human anti-snake venom IgG antibodies in a previously bitten snake-handler,but no protection against local envenoming

We report a 60 year old male bitten by snakes from the Acanthophis genus (Death adder) on two occasions who developed high titres of human IgG antibodies to Acanthophis venom detected at the time of the second bite. The patient was bitten by Acanthophis antarcticus (common death adder) on the first occasion, developed non-specific systemic effects and did not receive antivenom. Three months later he was bitten by Acanthophis praelongus (northern death adder) and he developed significant local myotoxicity associated with a moderate rise in the creatine kinase (maximum 4770 U/L). He was given antivenom 55 h after the bite and recovered over several days. Death adder venom was detected in serum at the time of the first bite, but not the second bite. Human IgG antibodies to death adder were detected on the second admission but not the first. However, despite the presence of antibodies to death adder venom and free venom not being detected, the patient still developed significant local myotoxicity.     

Depression, hopelessness, and sleep in cancer patients' desire for death

OBJECTIVE: The aim of this study was to evaluate the prevalence of clinical characteristics and risk factors for hastened death in advanced cancer patients. METHODS: Patients completed the Greek version of Schedule of Attitudes toward Hastened Death (G-SAHD), a sleep quality measure, the Pittsburgh Sleep Quality Index (PSQI), a Greek version of a depression inventory, the Beck Depression Inventory (BDI), a hopelessness scale, the Beck Hopelessness Scale (BHS), and a Visual Analogue Scale (VAS) for the assessment of pain. PATIENTS: The final sample consisted of 102 terminally ill cancer patients attending a Palliative Care Unit. RESULTS: Statistically significant associations were found between G-SAHD and patients performance status (ECOG) (chi2 = 8.62, p = 0.003). Strongest associations were observed between desire for death, depression, and hopelessness (r = 0.468, p < 0.0005, r = 0.678, p < 0.0005, respectively). In the prediction of G-SHAD the contribution of "hopelessness" (p < 0.0005), "depression" (p < 0.0005), "use of sleeping medication" (p < 0.0005), and "sleep quality" (p = 0.001) was high (59% of variance). CONCLUSION: Depression, hopelessness, and sleep quality appeared to have a statistically significant relationship with desire for hastened death. Health care professionals finding desire for death in advanced cancer patients should not only consider depression and hopelessness, but also other factors such as poor sleep quality in their diagnostic formulations in order to provide the appropriate treatment.     

PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors

PTEN (phosphatase and tensin homolog) loss of function is the most common genetic aberration in endometrioid endometrial carcinomas. In addition to its well-described role in cell signaling, PTEN is involved in the maintenance of genomic stability. Loss of PTEN function causes defects in repair of DNA double-strand breaks by homologous recombination and, therefore, sensitizes cells to inhibition of the poly(adenosine diphosphate ribose) polymerase (PARP). Here, we determined the PTEN status of eight endometrioid endometrial carcinoma cell lines and correlated it with in vitro sensitivity to the PARP inhibitor KU0058948. PTEN-deficient cells showed a significantly greater sensitivity to KU0058948 than the two endometrioid endometrial carcinoma cell lines with wild-type PTEN. The cell lines lacking PTEN expression were unable to elicit a homologous recombination damage response as assayed by RAD51 focus function (a marker of competent homologous recombination DNA repair) upon irradiation and treatment with PARP inhibitors. PTEN silencing in PTEN wild-type Hec-1b cells resulted in reduced RAD51 foci formation after DNA damage and increased sensitivity to PARP inhibition. PTEN reexpression in PTEN-null cell lines resulted in enhanced RAD51 foci formation and in relative resistance to KU0058948. Given that up to 80% of endometrioid endometrial cancers lack PTEN expression, our results suggest that PARP inhibitors may be therapeutically useful for a subset of endometrioid endometrial cancers.