Cancer mortality for a single race in low versus high elevation counties in the u.s

A previous study compared cancer mortality in the six lowest versus six highest elevations in the U.S. for all races. This study looks at a single race since death rates tend to vary by race. In this ecological study, cancer mortality rates were compared between low and high states for a race that had sufficient number of counties reporting mortality data, that is, the white race. The average cancer mortality rate for low elevation counties was 73.47 + 18.35 compared to 53.90 + 13.76 for high elevation counties, a difference that was statistically significant (p < 0.0001), with a very large effect size (of 1.2). Higher elevation counties showed less cancer mortality rates for a single race compared to lower elevation counties, suggesting the presence of radiation hormesis. Further rigorous research is indicated to verify or refute these findings.     

Heart Disease Death Rates in Low Versus High Land Elevation Counties in the U.S

Previous research on land elevation and cancer death rates in the U.S. revealed lower cancer death rates in higher elevations. The present study further tests the possible effect of land elevation on a diffident health outcome, namely, heart disease death rates. U.S. counties not overlapping in their land elevations according to their lowest and highest elevation points were identified. Using an ecological design, heart disease death rates for two races (black and white) corresponding to lower elevation counties were compared to heart disease death rates in higher land elevation counties using the two-sample t-test and effect size statistics. Death rates in higher land elevation counties for both races were lower compared to the death rates in lower land elevation counties (p < 0.001) with large effect sizes (of > 0.70). Since this is an observational study, no causal inference is claimed, and further research is indicated to verify these findings.     

Mean cancer mortality rates in low versus high elevation counties in Texas

There is controversy as to whether low levels of radiation (i.e., < 5 rem) pose a health risk. This brief inquiry compares archived cancer mortality data in counties having relatively low (0-250 feet above sea level), medium (500-1000 feet above sea level), and high (3000+ feet above sea level) elevations also having corresponding greater natural background levels of radiation respectively. Cancer mortality was found to be lowest in the high elevation counties (mean = 58.2) followed by low elevation counties (67.5) and then medium elevation counties (70.4). Statistically significant differences were found between low -high elevations (p = 0.003), and medium - high elevations (p = 0.010), but not between low and medium elevations (p = 0.5). More rigorous research, with an accounting of confounding variables, is indicated.     

Cancer mortality, state mean elevations, and other selected predictors

This ecological inquiry compares cancer mortality rates in the U.S. to the predictor of natural background radiation (via land elevation means) along with eight other predictors thought to be associated with cancer mortality. Age-adjusted cancer mortality in 2006 was compared to the predictors of mean land elevation, percent of smokers, educational attainment, percent of population without health insurance, income, obesity, health perception, physical activity, and diet. Among the six predictors considered appropriate for multiple linear regression, three were found to be statistically significant; from strongest to weakest, these three were: smoking, land elevation, and educational attainment. The predictors of smoking and educational attainment have long been considered associated with cancer mortality. The finding that the predictor of land elevation / natural background radiation is inversely related to cancer mortality is another piece of evidence supporting the theory of radiation hormesis. In this study, land elevation / natural background radiation ranked second in predictive strength regarding cancer mortality, behind smoking and ahead of educational attainment. Since this is an ecological inquiry, no causal inferences can be made.     

Evidence Supporting Radiation Hormesis in Atomic Bomb Survivor Cancer Mortality Data

A recent update on the atomic bomb survivor cancer mortality data has concluded that excess relative risk (ERR) for solid cancers increases linearly with dose and that zero dose is the best estimate for the threshold, apparently validating the present use of the linear no threshold (LNT) model for estimating the cancer risk from low dose radiation. A major flaw in the standard ERR formalism for estimating cancer risk from radiation (and other carcinogens) is that it ignores the potential for a large systematic bias in the measured baseline cancer mortality rate, which can have a major effect on the ERR values. Cancer rates are highly variable from year to year and between adjacent regions and so the likelihood of such a bias is high. Calculations show that a correction for such a bias can lower the ERRs in the atomic bomb survivor data to negative values for intermediate doses. This is consistent with the phenomenon of radiation hormesis, providing a rational explanation for the decreased risk of cancer observed at intermediate doses for which there is no explanation based on the LNT model. The recent atomic bomb survivor data provides additional evidence for radiation hormesis in humans.     

Land Elevation and Cancer Mortality in U.S. Cities and Counties Using Median Elevations Derived from Geographic Information Systems

There are a number of variables that are correlated with land elevation. Land elevation, and in particular, its surrogate variables such as natural background radiation, can be studied in relation to cancer rates. The present ecological study focuses on three such variables correlated with land elevation: natural background radiation (NBR), oxygen concentration (OC), and barometric pressure (BP). In addition, the study uses a novel approach for determining median land elevation values from which the surrogated variables are estimated. Inverse correlations were observed for NBR while direct correlations were found for OC and BP suggesting the presence of a protective effect with all three variables. Further study is indicated to either verify or refute these findings.     

Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits

This study compares the chronic toxicity of two anthracyclines--daunorubicin and doxorubicin, commonly used for induction of anthracycline cardiomyopathy in the rabbit model. Such a comparative study has not been published until now. Both drugs were administered intravenously to male Chinchilla rabbits in doses at 3 mg/kg (50 mg/m2) once weekly for 10 weeks. Selected biochemical, haematological and cardiovascular parameters and body weights were regularly monitored; additionally, a histological evaluation of heart, kidney and liver was performed at the end of the experiment. In the daunorubicin group, there were marked signs of the progressive development of heart failure, like the significant increases of the pre-ejection period/left ventricular ejection time index values (up to 134%)--and histological changes within the myocardium were also observed. On the other hand, the 10-week doxorubicin administration did not cause these changes that are typical for heart injury. Haematotoxicity, manifested particularly by aplastic anaemia, was apparent in both the experimental groups. Significant body weight loss (by 45.2%) and high premature mortality (100% versus 36.4%) reflected a greater general toxicity, especially nephrotoxicity of doxorubicin in comparison with daunorubicin. Further studies are necessary to find a possible explanation for these findings.     

Oesophagectomy for carcinoma of the oesophagus--early results

Oesophagectomy for squamous cell carcinoma of the oesophagus was performed in 25 consecutive patients over a 3.5 years period, for an overall resection rate of 11 pc. It was an Ivor-Lewis in 19 and a left thoracotomy in six. The stage of the disease was II in two, III in six and IV in 17 cases. Seventeen patients had uneventful postoperative evolution. Complications occurred in eight patients: heart failure in three, anastomotic leak in three, massive chest wall infection in two and four of these patients died: a mortality rate of 16 pc. All the 21 patients who left the hospital were able to take normal diet. The mortality of oesophagectomy for cancer can be as high as 30 pc but decreases with better selection of patients and surgical experience. Cure is rarely achieved. Resective surgery, when successful, offers the best palliation for dysphagia. Resectability rate in all African series is very low. There is a need for a more aggressive surgery therapeutic attitude. Our series shows that it is possible in our environment to achieve an acceptable operative morbidity and mortality. With increasing experience, results can only improve.     

The Cancer Mortality in High Natural Radiation Areas in Poland

The cancer mortality ratios (CMRs) in Poland in high and low level radiation areas were analyzed based on information from national cancer registry. Presented ecological study concerned six regions, extending from the largest administration areas (a group of voivodeships), to the smallest regions (single counties). The data show that the relative risk of cancer deaths is lower in the higher radiation level areas. The decrease by 1.17%/mSv/year (p = 0.02) of all cancer deaths and by 0.82%/mSv/year (p = 0.2) of lung cancers only are observed.Tribute to Prof. Zbigniew Jaworowski (1927–2011)     

Investigational CETP antagonists for hyperlipidemia and atherosclerosis prevention

INTRODUCTION: Reverse cholesterol transport (RCT) is a function of high-density lipoproteins (HDL) in humans and higher species. It is enabled by the cholesteryl ester transfer protein (CETP), a high molecular weight protein exchanging cholesteryl esters in HDL for triglycerides in very low-density lipoproteins (VLDL). Inhibition of CETP may provide a useful strategy to raise HDL, the protective lipoprotein fraction in plasma. AREAS COVERED: Evaluation based on clinical and experimental findings of the three drugs developed or in advanced development for CETP inhibition. EXPERT OPINION: Inhibition of CETP, both inherited and drug induced, at times leads to dramatic elevations of HDL-cholesterol (HDL-C) levels. Epidemiological data presently available do not, however, provide convincing evidence that reduced CETP levels or activity due to genetic factors and associated with HDL-C elevations, reduce cardiovascular risk. Indeed, the opposite may be true in some instances. All the three CETP inhibitors were the object of experimental and clinical evaluation. Large clinical trials with torcetrapib led to very negative findings, that is, raised cardiovascular morbidity and mortality in addition to raised risk of cancer and sepsis. Off-target effects of the drug, such as aldosterone retention and raised blood pressure, were believed to provide an explanation for these negative findings. The two newer agents, dalcetrapib and anacetrapib, do not exert off-target effects. The two drugs differ because anacetrapib has a more dramatic effect on HDL cholesterolemia (+139%) versus more moderate effects of dalcetrapib (+20-30%). Anacetrapib, however, may impair formation of pre-β HDL, that is, the primary particles in the process of cholesterol removal. The initial large trial with anacetrapib (DEFINE study) in coronary patients on statin treatment, appeared to confirm a remarkable HDL raising property, together with some reduction in vascular end points, in particular coronary procedures. The issue of other potentially harmful effects of CETP inhibition (sepsis and others) has yet to be clarified. Large clinical end-point trials, however, will be necessary to provide convincing evidence that, in addition to raising HDL-C, CETP inhibitors provide a valid additional treatment, for example, to statins in patients with coronary heart disease (CHD) or at high risk of CHD.     

进驻高原健康青年血清白细胞介素—2的活性变化

探讨进驻高原不同海拔高度不同时间健康青年血清白细胞介素— 2 (IL— 2 )的活性变化。方法 :对从平原 (海拔 1 4 0 0m)进驻海拔 370 0m和 5380m高原第 7天和半年的某部 56名官兵 ,采用放射免疫法进行IL— 2测定 ,并以平原 2 8名健康青年作对照。结果 :初入海拔 5380m高原第 7天及居住半年时IL— 2活性较平原降低差异显著 (P <0 0 5或P <0 0 1 ) ;370 0m居住半年时变化无统计学差异 (P >0 0 5)。初入高原第 7天 ,海拔 5380m较 370 0mIL— 2降低差异非常显著(P <0 0 1 ) ;高原居住半年时 ,5380m较 370 0mIL— 2降低差异显著 (P <0 0 5)。进驻海拔 370 0m ,第 7天较半年IL— 2无显著性差异 (P >0 0 5) ;进驻海拔 5380m ,第7天较半年IL— 2降低差异有显著性 (P <0 0 5)。结论 :高原低氧 ,IL— 2水平降低引起免疫调节降低 ,导致免疫功能紊乱。     

Radiobiological basis of low-dose irradiation in prevention and therapy of cancer

Antimutagenic DNA damage-control is the central component of the homeostatic control essential for survival. Over eons of time, this complex DNA damage-control system evolved to control the vast number of DNA alterations produced by reactive oxygen species (ROS), generated principally by leakage of free radicals from mitochondrial metabolism of oxygen. Aging, mortality and cancer mortality are generally accepted to be associated with stem cell accumulation of permanent alterations of DNA, i.e., the accumulation of mutations. In a young adult, living in a low LET background of 0.1 cGy/y, the antimutagenic system of prevention, repair and removal of DNA alterations reduces about one million DNA alterations/cell/d to about one mutation/cell/d. DNA alterations from background radiation produce about one additional mutation per 10 million cells/d. As mutations accumulate and gradually degrade the antimutagenic system, aging progresses at an increasing rate, mortality increases correspondingly, and cancer increases at about the fourth power of age. During the past three decades, genomic, cellular, animal and human data have shown that low-dose ionizing radiation, including acute doses up to 30 cGy, stimulates each component of the homeostatic antimutagenic control system of antioxidant prevention, enzymatic repair, and immunologic and apoptotic removal of DNA alterations. On the other hand, high-dose ionizing radiation suppresses each of these antimutagenic protective components. Populations living in high background radiation areas and nuclear workers with increased radiation exposure show lower mortality and decreased cancer mortality than the corresponding populations living in low background radiation areas and nuclear workers without increased radiation exposure. Both studies of cancer in animals and clinical trials of patients with cancer also show, with high statistical confidence, the beneficial effects of low-dose radiation.     

A review of the ethnic differences in breast cancer

Women of African descent have a lower incidence of breast cancer than their white counterparts; however, the overall age-adjusted breast cancer mortality rates are higher. They also present at a younger age, and have more advanced disease that exhibits poor prognostic features including significantly larger tumors of higher grade, higher rates of estrogen receptor and progesterone receptor negativity and a higher rate of p53 mutations and HRAS1 proto-oncogene expression, all of which confer a poor prognosis. While there are many possible contributory factors to the discrepancies in outcome in women of African descent, there is no satisfactory explanation as to why women of African origin tend to present at a younger age with hormone receptor-negative tumors and more adverse prognostic features.     

Embryotoxic effects of L-691,121, a class III antiarrhythmic agent,in rats

 L-691,121 is a class III antiarrhythmic agent which blocks potassium currents, leading to prolongation of cardiac potential and prevention of cardiac arrhythmia. In a developmental toxicity study in rats, there was a dose-dependent decrease in embryonic/fetal survival, and death of the entire litter was seen at an oral dose of 0.8 mg/kg per day. The critical period for embryolethality was determined as gestational days (GD) 10–13. In a study where females received 1 mg/kg on a critical day (GD 10 or 12) and were killed at 24-h intervals, a high embryonic mortality was seen at 72 h (GD 10 treatment) or 48 h (GD 12 treatment) after dosing. The surviving embryos had morphological abnormalities such as enlarged cardiac tube and pericardium, generalized edema, and hematoma. In order to investigate a possible mechanism for the embryolethality, GD 11 embryos were dissected from females at 4 h after dosing of 1 mg/kg and incubated for 5 h in vitro. The embryonic heart rates were decreased for the first 2 h after incubation but tended to recover to control levels thereafter. When GD 11 embryos were incubated for 4 h with the drug, there were decreases in the heart rates during the entire observation period. In a wash-out study where the embryos were transferred to drug-free medium after 1-h exposure, decreased heart rates recovered to control levels. In GD 11 embryos cultured for 24 h with the drug, there were gross abnormalities that consisted of altered yolk sac and embryonic circulation, and enlargement of cardiac tube and pericardium similar to those seen in the preceding in vivo study. These results suggest that decreased heart rates, reduced yolk sac circulation and the associated morphological abnormalities induced by L-691,121 are related to the embryolethality in rats. Received: 14 December 1993 / Accepted: 16 March 1994     

Atomic Bomb Survivors Life-Span Study: Insufficient Statistical Power to Select Radiation Carcinogenesis Model

The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis. This paper shows that this claim is baseless. The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 0.3 Sievert (Sv) and saturation level at about 1.5 Sv. A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH. Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 2.5% per Sv, i.e., an increase of cancer mortality from about 20% spontaneous mortality to about 22.5% per Sv, which is about half of the usually cited value. The impact of the “neutron discrepancy problem” – the apparent difference between the calculated and measured values of neutron flux in Hiroshima – was studied and found to be marginal. Major revision of the radiation risk assessment paradigm is required.     

Need to change the direction of cholesterol-related medication--a problem of great urgency

The cholesterol hypothesis implies that reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are effective in lowering serum total cholesterol (TC), and thereby reducing the incidence of coronary heart disease (CHD). However, these dietary recommendations are essentially ineffective in reducing TC in the long run, but rather increase mortality rates from CHD and all causes. The reported "apparent relative risk of high TC in CHD mortality" (the ratio of mortality at the highest/lowest TC levels) varied several-fold among populations studied. The incidence of familial hypercholesterolemia (FH) in a population was proposed to be a critical factor in the observed variability, which could be accounted for by assuming that 1) the high CHD mortality rate in high-TC groups is mainly a reflection of the incidence and severity of FH, and 2) high TC is not a causative factor of CHD in non-FH cases. This interpretation is supported by recent observations that high TC is not positively associated with high CHD mortality rates among general populations more than 40-50 years of age. More importantly, higher TC values are associated with lower cancer and all-cause mortality rates among these populations, in which relative proportions of FH are likely to be low (circa 0.2%). Although the effectiveness of statins in preventing CHD has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to TC values to less than approximately 260 mg/dl among the general population and the elderly. Instead, an unbalanced intake of omega6 over omega3 polyunsaturated fats favors the production of eicosanoids, the actions of which lead to the production of inflammatory and thrombotic lipid mediators and altered cellular signaling and gene expression, which are major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.     

Long-term morbidity and mortality trials with amlodipine

Prospective controlled clinical trials with cardiovascular events and mortality as end points are needed to provide clinicians with a fully informed choice of optimal hypertensive therapy. Seven trials (six of them still ongoing) have provided insight into the effects of the third-generation calcium antagonist, amlodipine, on mortality and end-organ damage in patients with hypertension or other forms of cardiovascular disease. The completed PRAISE study has addressed the safety of amlodipine in patients with advanced heart failure (CHF). The trial showed that amlodipine does not increase mortality or morbidity in CHF patients and significantly reduces the risk for these end points in patients whose CHF has a nonischemic etiology. The PRAISE-2 study is now under way to further evaluate the benefits of amlodipine in nonischemic CHF patients. The ALLHAT trial compares the effects of standard diuretic treatment with three alternative treatments (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in 40,000 hypertensive patients. The ASCOT trial compares the effects of amlodipine +/- perindopril with atenolol +/- bendrofluazide on fatal CAD and nonfatal MI in 18,000 high-risk patients. The PREVENT trial tests a similar hypothesis, looking at the effects of amlodipine on arterial atherosclerotic lesions, and the AASK trial is evaluating the effects of amlodipine on renal disease. The PRAISE trial has provided valuable information on the safety and efficacy of amlodipine in preventing death and disability in patients with CHF. The six ongoing trials will provide important additional information on the effect of amlodipine in patients with heart disease of other etiologies.     

Cardiovascular disease mortality trends in the western Pacific, 1968-1984

Much attention has been paid in recent years to the declining cardiovascular disease mortality rates in western industrialised countries; far less attention has been paid to other countries. A comparison of 1984 age standardised mortality rates in five western Pacific countries indicates a wide variation for all cause mortality and all cardiovascular disease mortality, with Singapore having rates twice as great as Japan which has the lowest rates. New Zealand has the highest rate of coronary heart disease, and with Australia the lowest rate of stroke mortality. Mortality rates for each disease category studied were lower among women than men for each country. In the period 1968-1984 all countries experienced a decline in all cause mortality. All cardiovascular disease mortality rates have declined in all countries except Singapore; coronary heart disease mortality rates have increased in Singapore. The improvements in stroke mortality in Japan have been dramatic in comparison with the other four countries. These marked variations in absolute levels and secular trends raise intriguing research questions and indicate the potential for prevention in all countries.     

Adrenomedullary and beta-adrenergic participation in enhanced sympathetic pressor responses of spontaneously hypertensive rats

The beta-adrenergic and adrenomedullary components of pressor responses to sympathetic nerve stimulation were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The effects of electrical stimulation of the entire spinal cord of pithed rats pretreated with tubocurarine and atropine were studied on systolic blood pressure, heart rate and plasma cyclic AMP levels. The heart rate increase upon low frequency stimulation (1 Hz) and the blood pressure elevation upon stimulation at higher frequencies (3 and 5 Hz) were higher in SHR than in WKY whereas the increase in circulating cyclic AMP level was not different in the two strains. Pretreatment with propranolol (2.5 mg X kg-1) further enhanced the pressor responses in SHR but not in WKY, although it inhibited the heart rate acceleration and decreased the circulating level of cyclic AMP similarly in the two strains. After acute adrenalectomy, the elevations of blood pressure and circulating cyclic AMP levels were reduced to an identical level in SHR and WKY. These results show that the marked enhancement of the pressor response observed in SHR upon stimulation of the entire sympathetic outflow is mostly of adrenomedullary origin and includes a hypotensive component due to beta-adrenoceptor stimulation which is not present in WKY.