Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology

A case–control study of risk of leukaemia in relation to mobile phone use

Background Mobile phone use is now ubiquitous, and scientific reviews have recommended research into its relation to leukaemia risk, but no large studies have been conducted.Methods In a case-control study in South East England to investigate the relation of acute and non-lymphocytic leukaemia risk to mobile phone use, 806 cases with leukaemia incident 2003-2009 at ages 18-59 years (50% of those identified as eligible) and 585 non-blood relatives as controls (provided by 392 cases) were interviewed about mobile phone use and other potentially aetiological variables.Results No association was found between regular mobile phone use and risk of leukaemia (odds ratio (OR)=1.06, 95% confidence interval (CI)=0.76, 1.46). Analyses of risk in relation to years since first use, lifetime years of use, cumulative number of calls and cumulative hours of use produced no significantly raised risks, and there was no evidence of any trends. A non-significantly raised risk was found in people who first used a phone 15 or more years ago (OR=1.87, 95% CI=0.96, 3.63). Separate analyses of analogue and digital phone use and leukaemia subtype produced similar results to those overall.Conclusion This study suggests that use of mobile phones does not increase leukaemia risk, although the possibility of an effect after long-term use, while biologically unlikely, remains open

Review of epidemiologic data on the debate over smokeless tobacco's role in harm reduction

Some tobacco researchers have argued that the European Union should remove its ban on a form of low-nitrosamine smokeless tobacco referred to as Swedish 'snus'. This argument has developed in to an international debate over the use of smokeless tobacco as a measure of harm reduction for smokers. Leading authorities in the USA have firmly stated that there is no safe tobacco - a message which does not allow for any discussion of comparative tobacco risks. This commentary is intended to review the origin of the controversy over Swedish 'snus', to examine briefly the meta-analysis on cancer risks by Peter Lee and Jan Hamling (published in July in BMC Medicine) and to discuss the anticipated direction of the debate on tobacco-harm reduction in the USA. We anticipate that much of the debate will shift from the discussion of epidemiologic data to the discussion of the marketing, health communication and economics of smokeless tobacco. While the Food and Drug Administration's newly approved authority over tobacco will undoubtedly affect the smokeless products, it may not be the sole determinant of harm reduction's fate in the USA

Impact of alcohol drinking on total cancer risk: data from a large-scale population-based cohort study in Japan

We conducted a cohort study of alcohol consumption and total cancer incidence and mortality in 73 281 subjects (35 007 men and 38 274 women) aged 40–59 years old at baseline over a 10-year follow-up period. During 1990–2001, a total of 3403 cases of newly diagnosed cancer and 1208 cancer deaths were identified. In men, the lowest risk of developing cancer was observed among occasional drinkers, and a linear positive association with increased ethanol intake was noted (hazard ratio 1.18 for 1–149 g per week, 1.17 for 150–299 g per week, 1.43 for 300–449 g per week, 1.61 for ⩾450 g per week, P for trend <0.001). The positive relation was similar for cancer incidence and mortality, but was more striking among current smokers and alcohol-related cancers. Relatively few women were regular drinkers. Our results suggest that increased ethanol intake linearly elevates the risk of cancer, and that nearly 13% of cancers among males in this study were due to heavy drinking (⩾300 g per week of ethanol), to which smoking substantially contributed. The simultaneous reduction of smoking is therefore important for reducing the effect of alcohol on cancer risk

Mortality among Norwegian doctors 1960-2000

<p>Abstract</p> <p>Background</p> <p>To study the mortality pattern of Norwegian doctors, people in human service occupations, other graduates and the general population during the period 1960-2000 by decade, gender and age. The total number of deaths in the study population was 1 583 559.</p> <p>Methods</p> <p>Census data from 1960, 1970, 1980 and 1990 relating to education were linked to data on 14 main causes of death from Statistics Norway, followed up for two five-year periods after census, and analyzed as stratified incidence-rate data. Mortality rate ratios were computed as combined Mantel-Haenzel estimates for each sex, adjusting for both age and period when appropriate.</p> <p>Results</p> <p>The doctors had a lower mortality rate than the general population for all causes of death except suicide. The mortality rate ratios for other graduates and human service occupations were 0.7-0.8 compared with the general population. However, doctors have a higher mortality than other graduates. The lowest estimates of mortality for doctors were for endocrine, nutritional and metabolic diseases, diseases in the urogenital tract or genitalia, digestive diseases and sudden death, for which the numbers were nearly half of those for the general population. The differences in mortality between doctors and the general population increased during the periods.</p> <p>Conclusions</p> <p>Between 1960 and 2000 mortality for doctors converged towards the mortality for other university graduates and for people in human service occupations. However, there was a parallel increase in the gap between these groups and the rest of the population. The slightly higher mortality for doctors compared with mortality for other university graduates may be explained by the higher suicide rate for doctors.</p

Alcohol and cardio-respiratory deaths in Chinese: a population-based case-control study of 32,462 older Hong Kong adults

Background: In observational studies moderate alcohol use reduces cardio-respiratory mortality. However observational studies may be biased by many factors including residual confounding by unmeasured differences between moderate alcohol users and other groups or by changes in alcohol use with ill-health and aging. We used two different analytic strategies in an under-studied population, i.e. southern Chinese, to provide an assessment of the specific impact of moderate alcohol use on mortality from ischemic heart disease (IHD) and chronic obstructive pulmonary diseases (COPD). Methods: In a population-based case-control study of all adult deaths in Hong Kong Chinese in 1998, we used adjusted logistic regression to compare alcohol use in decedents aged ≥ 60 years from IHD (2270) and COPD (1441) with 10,320 living and 9043 dead controls (all non-alcohol related deaths). We also examined whether the association of alcohol use with death from IHD or COPD varied with sex or smoking status. Results: Using living controls and adjusted for age, socio-economic status and lifestyle, occasional and moderate alcohol use were generally associated with lower mortality from IHD and COPD. However, using dead controls the protection of occasional and moderate alcohol use appeared to be limited to ever-smokers for IHD (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.46 to 0.73 for moderate compared to never-use in ever-smokers, but OR 1.07, 95% CI 0.76 to 1.50 in never-smokers), and possibly to men for COPD. High alcohol use was associated with lower IHD mortality and possibly with lower COPD mortality. Conclusion: High levels of alcohol use in an older Chinese population were associated with lower IHD mortality. Moderate alcohol use was less consistently protective against IHD mortality. Alcohol use was associated with lower COPD mortality particularly in men, either due to some yet to be clarified properties of alcohol or as the artefactual result of genetic selection into alcohol use in a Chinese population. Given the increasing use of alcohol in China with economic development, other designs and analytic strategies are needed to assess the impact of alcohol in this population, so that an evidence-based public health policy can be formulated.link_to_subscribed_fulltex

Moderate alcohol consumption is associated with better endothelial function: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Moderate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery in humans.</p> <p>Methods</p> <p>In the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%).</p> <p>Results</p> <p>The mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5%) (unadjusted OR 1.7, 95% CI 1.2–2.4, p = 0.005). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95%CI 1.1–3.0, p = 0.03). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day.</p> <p>Conclusion</p> <p>In conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.</p

Methodologies used to estimate tobacco-attributable mortality: a review

<p>Abstract</p> <p>Background</p> <p>One of the most important measures for ascertaining the impact of tobacco on a population is the estimation of the mortality attributable to its use. To measure this, a number of indirect methods of quantification are available, yet there is no consensus as to which furnishes the best information. This study sought to provide a critical overview of the different methods of attribution of mortality due to tobacco consumption.</p> <p>Method</p> <p>A search was made in the Medline database until March 2005 in order to obtain papers that addressed the methodology employed for attributing mortality to tobacco use.</p> <p>Results</p> <p>Of the total of 7 methods obtained, the most widely used were the prevalence methods, followed by the approach proposed by Peto et al, with the remainder being used in a minority of studies.</p> <p>Conclusion</p> <p>Different methodologies are used to estimate tobacco attributable mortality, but their methodological foundations are quite similar in all. Mainly, they are based on the calculation of proportional attributable fractions. All methods show limitations of one type or another, sometimes common to all methods and sometimes specific.</p

An international review of tobacco smoking in the medical profession: 1974–2004

Background\ud Tobacco smoking by physicians represents a contentious issue in public health, and regardless of what country it originates from, the need for accurate, historical data is paramount. As such, this article provides an international comparison of all modern literature describing the tobacco smoking habits of contemporary physicians.\ud \ud Methods\ud A keyword search of appropriate MeSH terms was initially undertaken to identify relevant material, after which the reference lists of manuscripts were also examined to locate further publications.\ud \ud Results\ud A total of 81 English-language studies published in the past 30 years met the inclusion criteria. Two distinct trends were evident. Firstly, most developed countries have shown a steady decline in physicians' smoking rates during recent years. On the other hand, physicians in some developed countries and newly-developing regions still appear to be smoking at high rates. The lowest smoking prevalence rates were consistently documented in the United States, Australia and the United Kingdom. Comparison with other health professionals suggests that fewer physicians smoke when compared to nurses, and sometimes less often than dentists.\ud \ud Conclusion\ud Overall, this review suggests that while physicians' smoking habits appear to vary from region to region, they are not uniformly low when viewed from an international perspective. It is important that smoking in the medical profession declines in future years, so that physicians can remain at the forefront of anti-smoking programs and lead the way as public health exemplars in the 21st century