Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results.

PURPOSE: To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC. METHODS: A survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c). RESULTS: Mean follow-up time for all patients was 68 months (range: 5-288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3­year cancer-specific survival was 23% with SPC. CONCLUSION: According to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.

Molecular cloning, mRNA expression and biological activity of the pheromone biosynthesis activating neuropeptide (PBAN) from the European corn borer, Ostrinia nubilalis.

Pheromone biosynthesis activating neuropeptide (PBAN) is a member of the pyrokinin (FXPRLamide) insect neuropeptides. Here, we report the cloning of the gene Ostnu-PBAN from the E and Z pheromone strains of the European corn borer (ECB), Ostrinia nubilalis (Lepidoptera: Crambidae), a major pest of maize. The Ostnu-PBAN genomic sequence is > 5 kb in length and consists of six exons. The deduced amino acid sequence revealed a 200-residue precursor protein including a signal peptide, a 24-amino acid (aa) diapause hormone, a 37-aa PBAN and three other FXPRLamide neuropeptides. Our in vivo assays suggest that the 37-aa synthetic Ostnu-PBAN is hormonally active in the pheromone gland. It restores sex pheromone production to normal levels in mated females and decapitated virgins of both E and Z cultures. The results of a real-time PCR analysis indicated that Ostnu-PBAN mRNA levels reached a plateau in the brain-suboesophageal ganglion complexes 1 day after eclosion, and mating did not affect the mRNA expression. Three size classes of Ostnu-PBAN mRNA (1.9, 2.0 and 2.1 kb) were obtained, differing only in the length of the 3' untranslated region. However, there was no correlation between sequence divergence and the pheromone composition, voltinism or geographical origin (Hungary, Slovenia, Sweden, Turkey) of ECB moths.

Short-term effects of T-2 toxin exposure on some lipid peroxide and glutathione redox parameters of broiler chickens.

The purpose of this study was to investigate the short-term effects of T-2 toxin exposure (3.09 mg/kg feed) on lipid peroxidation and glutathione redox system of broiler chicken. A total of 54 Cobb 500 cockerels were randomly distributed to two experimental groups at 21 days of age. Samples (blood plasma, red blood cell, liver, kidney and spleen) were collected every 12 h during a 48-h period. The results showed that the initial phase of lipid peroxidation, as measured by conjugated dienes and trienes in the liver, was continuously, but not significantly higher in T-2 toxin-dosed birds than in control birds. The termination phase of lipid peroxidation, as measured by malondialdehyde, was significantly higher in liver and kidney as a result of T-2 toxin exposure at the end of the experimental period (48th hour). The glutathione redox system activated shortly after starting the T-2 toxin exposure, which is supported by the significantly higher concentration of reduced glutathione and glutathione peroxidase activity in blood plasma at 24 and 48 h, in liver at 12, 24 and 36 h, and in kidney and spleen at 24 h. These results suggest that T-2 toxin, or its metabolites, may be involved in the generation of reactive oxygen substances which causes an increase in lipid peroxidation, and consequently activates the glutathione redox system, namely synthesis of reduced glutathione and glutathione peroxidase.

Heat shock-induced enhanced susceptibility of barley to Bipolaris sorokiniana is associated with elevated ROS production and plant defence-related gene expression.

Heat stress alters plant defence responses to pathogens. Short-term heat shock promotes infections by biotrophic pathogens. However, little is known about how heat shock affects infection by hemibiotrophic pathogens like Bipolaris sorokiniana (teleomorph: Cochliobolus sativus). We assessed the effect of heat shock in B. sorokiniana-susceptible barley (Hordeum vulgare cv. Ingrid) by monitoring leaf spot symptoms, B. sorokiniana biomass, ROS and plant defence-related gene expression following pre-exposure to heat shock. For heat shock, barley plants were kept at 49 °C for 20 s. B. sorokiniana biomass was assessed by qPCR, ROS levels determined by histochemical staining, while gene expression was assayed by RT-qPCR. Heat shock suppressed defence responses of barley to B. sorokiniana, resulting in more severe necrotic symptoms and increased fungal biomass, as compared to untreated plants. Heat shock-induced increased susceptibility was accompanied by significant increases in ROS (superoxide, H2 O2 ). Transient expression of plant defence-related antioxidant genes and a barley programmed cell death inhibitor (HvBI-1) were induced in response to heat shock. However, heat shock followed by B. sorokiniana infection caused further transient increases in expression of HvSOD and HvBI-1 correlated with enhanced susceptibility. Expression of the HvPR-1b gene encoding pathogenesis-related protein-1b increased several fold 24 h after B. sorokiniana infection, however, heat shock further increased transcript levels along with enhanced susceptibility. Heat shock induces enhanced susceptibility of barley to B. sorokiniana, associated with elevated ROS levels and expression of plant defence-related genes encoding antioxidants, a cell death inhibitor, and PR-1b. Our results may contribute to elucidating the influence of heat shock on barley defence responses to hemibiotrophic pathogens.

Population-based versus high-risk strategies for the prevention of cardiovascular diseases in low- and middle-income countries.

Cardiovascular diseases (CVD) are now the number one cause of death in low- and middle-income countries (LMIC), such as those in South East Asia (SEA). It is projected that SEA countries will have the greatest total number of deaths due to non-communicable diseases (NCDs) by 2020. In low resource countries, the rising burden of CVDs imposes severe economic consequences that range from impoverishment of families to high health system costs and the weakening of country economies. There are two possible options to be considered for addressing this issue: a "population-based strategy" and/or a "high risk" strategy. The question is, what is the optimal way to reduce the excessive burden of these diseases in the LMICs. We believe that by applying systematic policy and smoking cessation programs with proven effectiveness, there is a chance that the high smoking prevalence, particularly among SEA.

Time trends in cardiovascular and all-cause mortality in the 'old' and 'new' European Union countries.

AIMS: There are large differences in all-cause and cardiovascular disease (CVD) mortality between eastern and western countries in Europe. We reviewed the development of these mortality trends in countries of the European Union (EU) over the past 40 years and evaluated available data regarding possible determinants of these differences. METHODS AND RESULTS: We summarized all-cause mortality and specific cardiovascular mortality for two country groups - 10 countries that joined the European Union (EU) after 2004 (East), and 15 countries that joined before 2004 (West). Standardized mortality rates were retrieved from the World Health Organization "European Health for All" database for each country between 1970 and 2007. Currently (in the 2000s), mortality due to circulatory system disease, ischemic heart disease (IHD), cerebrovascular disease (CBVD), and all-causes in the 'new' EU countries (East) is approximately twice that in the 'old' EU countries (West). These differences were much smaller in the 1970s. The increasing gap in mortality between West and East is primarily the result of a continuous and rapid improvement in the West. CONCLUSION: Differences in lifestyle (i.e. diet, alcohol consumption, physical activity, and smoking) provide insufficient explanation for the observed mortality gap in these two groups of EU countries. Higher expenditures on health, better access to invasive and acute cardiac care, and better pharmacological control of hypertension and hypercholesterolemia in the West are well documented. Socioeconomic and psychosocial factors may also contribute to the changes in mortality trends.

Prognosis of patients with local recurrence after mastectomy or conservative surgery for early-stage invasive breast cancer.

Between 1983 and 1987, 1309 women with stage I or II breast cancer underwent mastectomy (n=894) or conservative surgery (CS, n=415). Of these patients, 124 developed an isolated local recurrence (ILR): chest wall, 56 and in-breast, 68. The 10-year actuarial rate of cause-specific survival after treatment for ILR was 52%. On multivariate analysis three independent prognostic factors for the risk of death after ILR were identified: operability of recurrence (operable vs. inoperable, relative risk [RR]: 5.9), age at initial diagnosis (>40 vs. < or = 40 years, RR: 2.2) and time to ILR (>24 vs. < or = 24 months, RR: 2). Initial lymph node stage (negative vs. positive) showed borderline significance (p=0.06), and type of initial surgery (CS vs. mastectomy) and recurrent tumor grade (1-2 vs. 3) were not independent predictors of survival. In the mastectomy group, single surgical scar recurrence with initial node negative stage predicted good prognosis, and the 10-year survival was 85%. In the CS group, the 10-year survival rate was 88% with new primary tumor and 54% with true recurrence (p=0.01), and the type of salvage surgery (mastectomy vs. repeat complete excision) had no significant impact on survival (p=0.2). The majority (n=44) of CS patients developed < or = 2 cm in-breast recurrence, and the 10-year survival was 81% after both salvage excision (n=28) and mastectomy (n=16). The identified unfavorable prognostic factors are pointers of the forthcoming systemic progression. Patients with < or = 2 cm in-breast recurrence might receive a second CS.

Toxicological effects of aflatoxin B1 on the earthworm Eisenia fetida as determined in a contact paper test.

In this study, aflatoxin B1 (AFB1) toxicity toward the earthworm Eisenia fetida (Savigny 1826) was evaluated in contact paper test systems containing distilled water and ethanol or 20 to 400 µg/ml of AFB1 over 72 h of exposure. The results indicated that AFB1 could induce significant damage to earthworms (coiling, curling, excessive mucus secretion, clitellum swelling) at greater than 75 µg/ml. Moreover, AFB1 had harmful effects on E. fetida (degenerative changes such as bulging of the clitella regions) at levels higher than 150 µg/ml. The calculated LD50 was 168.5 µg/ml. These findings confirm that E. fetida and standardized methods based on this organism (OECD 207 1984) are applicable and useful in mycotoxin related toxicity studies.

Alteration of sarcoplasmic reticulum Ca2+ ATPase expression in lower limb ischemia caused by atherosclerosis obliterans.

Atherosclerosis is a disease caused by a build-up of fatty plaques and cholesterol in the arteries. The lumen of the vessels is obliterated resulting in restricted blood supply to tissues. In ischemic conditions, the cytosolic Ca2+ level of skeletal muscle may increase, indicating the alteration of Ca2+ removal mechanisms. Ca2+ is transported from cytosol into the sarcoplasmic reticulum by Ca2+ ATPase (SERCA), with its 1a isoform expressed in adult, while its 1b isoform in neonatal and regenerating fast-twitch skeletal muscle. To investigate the role of these isoforms in ischemic skeletal muscle, biopsies from musculus biceps femoris of patients who underwent amputation due to atherosclerosis were examined. Samples were removed from the visibly healthy and hypoxia-affected tissue. Significantly increased SERCA1a expression was detected under the ischemic conditions (246 ± 69%; p < 0.05) compared with the healthy tissue. Furthermore, the ratio of SERCA1a-positive fibers was slightly increased (46 ± 4% in healthy tissue and 60 ± 5% in ischemic tissue; p > 0.05), whereas SERCA2a did not change. In addition, in primary cultures derived from hypoxia-affected tissue, the diameter and fusion index of myotubes were significantly increased (30 ± 1.6 µm vs. 41 ± 2.4 µm and 31 ± 4% vs. 45 ± 3%; p < 0.05). We propose that the increased SERCA1a expression indicates the existence and location of compensating mechanisms in ischemic muscle.

Worldwide epidemic of hypertension.

The World Health Report 2002 identified hypertension, or high blood pressure, as the third ranked factor for disability-adjusted life years. Hypertension is one of the primary risk factors for heart disease and stroke, the leading causes of death worldwide. Recent analyses have shown that as of the year 2000, there were 972 million people living with hypertension worldwide, and it is estimated that this number will escalate to more than 1.56 billion by the year 2025. Nearly two-thirds of hypertensives live in low- and middle-income countries, resulting in a huge economic burden. Awareness, prevention, treatment and control of hypertension is a significant public health measure. The World Hypertension League, through its national member societies, launched World Hypertension Day in 2005 and, due to its success throughout the world, it has been made an annual event. The 2006 World Hypertension Day was held on May 13; the theme of the day was "Treat to Goal", with a clear intent to ensure patient adherence and control of hypertension worldwide. In Canada, all stakeholders--professional societies, government, nongovernment organizations and industry--are working together to promote awareness of hypertension and to control it.

In vitro study of elements in herbal remedies.

Decreased glucose tolerance is a first sign of diabetes mellitus and therefore rigorous control must be taken in carbohydrate and lipid metabolisms. Herbal remedies (lyophilized extracts of Myrtilli folium and Phaseoli fructus sine seminibus (L1), Myrtilli folium, Phaseoli fructus sine seminibus, and Salviae folium (L2) are traditionally used in mid-European folk medicine and in common adjuvant therapy for the prevention of complications in type 2 diabetes. Significant iron (355.7 +/- 13.8 mg/kg) and zinc (84.73 +/- 1.83 mg/kg) concentration was found in L1 and chromium (3.82 +/- 2.71 mg/kg) in L2. Ion concentrations in teas made from L1 and L2 are relatively low because the quantities of metal ions in teas do not cover the daily need, although the teas are good sources for some elements. According to the Recommended Daily Allowances, the tea of L1 is a good source for iron and manganese, whereas for chromium, the tea of L2 is better. For evaluating the element bioavailability, an in vitro dialysis system was applied to determine the element transfer from tea of the lyophilized sample to the plasma (buffer pH=7.4). Measurements showed that the elements transferred between 6.90% (iron from tea of L2) and 90.05% (chromium from tea of L2) through the membrane from teas to the plasma. Metal ions in teas of herbal remedies might contribute to the favorable therapeutic effect of preventing complications, because they might transfer through the membranes in relatively high percentages.

Alkane isomers: presence in petroleum ether and complexity.

The presence and absence of alkane isomers in petroleum and petroleum derivatives depend on the complexity of these structures. It was assumed that the more complex the structure is the less probable it is that that the molecule can be detected in any petroleum derivative. Complexity is a vague concept, which has not been defined in quantitative terms yet, and therefore there is no experimental method, which could be used to determine 'complexity'. Mass spectrometry and infrared spectroscopy in combination with gas chromatography were used to identify the various structural isomers of alkanes in petroleum ether. The isomers were categorised in quantitative terms by using topological indices and linear discriminant analysis. It was found that alkanes possessing a more complex, highly branched structure are less probable to be detected in petroleum ether than isomers with a simpler backbone structure. It was proposed that the experimental 'measure' of the complexity of isomer(i) should be proportional to 1/C(i), where C(i), denotes the concentration of isomer(i) in a (primary) petroleum derivative.

Comparison of the amount of bioaccessible fumonisin B1 and B2 in maize and rice inoculated with Fusarium verticillioides (MRC 826) and determined by in vitro digestion-preliminary results.

In this study the occurrence of hidden fumonisin B1 (FB1) and fumonisin B2 (FB2) was analysed, on two cereal substrates (maize and rice), inoculated with Fusarium verticillioides (MRC 826), in order to determine the ratio of hidden FB1 and FB2. Two parallel methods were applied: an in vitro human digestion sample pre-treatment and the routine extraction procedure, in both cases with subsequent LC-MS analysis. It was found that all samples showed higher concentration of total fumonisin B1 after digestion, as compared to that of free fumonisin analysed only after extraction. The percentage of the hidden form by maize was 18.8 % (±2.4) for FB1 and 36.8 % (±3.8) for FB2, while for rice it was 32.3 % (±11.3) and 58.0 (±6.8), respectively, expressed as the proportion to total fumonisin B1, for the total dataset. Significant differences were found in the FB1 and FB2 concentration measured after the different digestion phases (saliva, gastric and duodenal) in case of both matrixes. The results are useful for human risk assessment, since both humans and animals may be exposed to markedly higher toxin load, as determined merely by conventional analytical methods.

Oral administration of fumonisin B1 and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits.

Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B1 (FB1) alone, and both toxins in combination (2 + 10 mg/kg, respectively) compared to a toxin-free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (threefold of control). Liver total phospholipids (PLs) provided slight alterations in the fatty acid (FA) composition; all three toxin-treated groups showed a decrease in palmitoleic acid (C16:1 n7) proportion. In the liver mitochondrial PL FA composition, margaric acid (C17:0) proportion decreased in the separated toxin treatments compared to the combined setting. Oleic acid (C18:1 n9) proportion was increased and arachidonic acid (C20:4 n6) was decreased in the FB1-treated group, while docosapentaenoic acid (C22:5 n3) was decreased in the separated treatments. The total monounsaturation was significantly higher in the FB1 group's mitochondrial PL FA profile. After 4 weeks, all toxin treatments decreased the blood plasma reduced glutathione and glutathione peroxidase activity, and FB1 increased the plasma sphinganine/sphingosine ratio. Both mycotoxins seem to cross the hepatocellular and the hepatic mitochondrial membrane, without drastic membrane disruption, as assessed from the PL FA composition, but inducing detectable lipid peroxidation.

Why are adult women physically active? A systematic review of prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants.

OBJECTIVE: This study aims to systematically review available evidence from prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants of moderate-to-vigorous intensity physical activity (MVPA) among working-age women. METHODS: Six databases were searched to identify all prospective cohort studies that reported on intrapersonal (e.g. self-efficacy and socioeconomic status [SES]), social (e.g. crime, area SES and social support) and/or physical (e.g. weather, work and recreation) environmental determinants of MVPA in working-age (mean 18-65 years) women. A qualitative synthesis including harvest plots was completed. PROSPERO: CRD42014009750 RESULTS: Searching identified 17,387 potential articles; 97 were used in the analysis. The majority (n = 87 studies) reported on ≥1 intrapersonal determinant. Very few (n = 34) examined factors in the social or physical environments, and none looked at social policy. Positive and consistent influencers included higher self-efficacy (n = 18/23), self-rated health (n = 8/13) and intentions (n = 10/11) and perceived behavioural control (n = 5/7) to be physically active. Having children in the household was negatively related to MVPA (n = 9/15). CONCLUSIONS: Physical activity intervention studies should consider a woman's level of self-efficacy and perceived behavioural control to be physically active. Additional studies are needed on the impact of children in the household, having a spouse/partner and using group goal setting. More evidence is needed to evaluate the impact of environmental factors.

Local and Systemic Responses of Antioxidants to Tobacco Mosaic Virus Infection and to Salicylic Acid in Tobacco (Role in Systemic Acquired Resistance).

Changes in ascorbate and glutathione levels and in activities of ascorbate peroxidase, catalase, dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD) were investigated in tobacco mosaic virus (TMV)-inoculated lower leaves and in non-inoculated upper leaves of Nicotiana tabacum L. cv Xanthi-nc. In separate experiments the effects of exogenous salicylic acid (SA) were also studied. Symptom appearance after TMV inoculation was preceded by a slight, transient decline of ascorbate peroxidase, GR, GST, and SOD activities in the inoculated lower leaves, but after the onset of necrosis these activities and the glutathione level substantially increased. Ascorbic acid level and DHAR activity declined and dehydroascorbate accumulated in the inoculated leaves. In upper leaves, the glutathione level and the activities of GR, GST, and SOD increased 10 to 14 d after TMV inoculation of the lower leaves, concomitantly with the development of systemic acquired resistance. From the six distinct SOD isoenzymes found in tobacco leaves, only the activities of Cu,Zn-SOD isoenzymes were affected by TMV. SA injection induced DHAR, GR, GST, and SOD activities. Catalase activities were not modified by TMV infection or SA treatment. It is supposed that stimulated antioxidative processes contribute to the suppression of necrotic symptom development in leaves with systemic acquired resistance.

Hypersensitive cell death and papilla formation in barley attacked by the powdery mildew fungus are associated with hydrogen peroxide but not with salicylic acid accumulation

We analyzed the pathogenesis-related generation of H2O2 using the microscopic detection of 3,3-diaminobenzidine polymerization in near-isogenic barley (Hordeum vulgare L.) lines carrying different powdery mildew (Blumeria graminis f.sp. hordei) resistance genes, and in a line expressing chemically activated resistance after treatment with 2,6-dichloroisonicotinic acid (DCINA). Hypersensitive cell death in Mla12 and Mlg genotypes or after chemical activation by DCINA was associated with H2O2 accumulation throughout attacked cells. Formation of cell wall appositions (papillae) mediated in Mlg and mlo5 genotypes and in DCINA-activated plants was paralleled by H2O2 accumulation in effective papillae and in cytosolic vesicles of up to 2 µm in diameter near the papillae. H2O2 was not detected in ineffective papillae of cells that had been successfully penetrated by the fungus. These findings support the hypothesis that H2O2 may play a substantial role in plant defense against the powdery mildew fungus. We did not detect any accumulation of salicylic acid in primary leaves after inoculation of the different barley genotypes, indicating that these defense responses neither relied on nor provoked salicylic acid accumulation in barley.

E-health physical activity interventions and moderate-to-vigorous intensity physical activity levels among working-age women: a systematic review protocol.

BACKGROUND: The rapid pace of modern life requires working-age women to juggle occupational, family, and social demands. Despite the large numbers of working-age women in developed countries and the proven benefits of regular moderate-to-vigorous intensity aerobic physical activity (MVPA) in chronic disease prevention, few women meet current physical activity (PA) recommendations of 150 min of MVPA per week. It is important that appropriate and effective behavioral interventions targeting PA are identified and developed to improve the MVPA levels of working-age women. As women worldwide embrace modern technologies, e-health innovations may provide opportune and convenient methods of implementing programs and strategies to target PA in an effort to improve MVPA levels and cardiometabolic health. Previous reviews on this topic have been limited; none have focused on working-age women from developed countries who exhibit inappropriately low PA levels. It remains unknown as to which e-health interventions are most effective at increasing MVPA levels in this population. The purpose of this systematic review is to examine the effectiveness of e-health interventions in raising MVPA levels among working-age women in developed countries and to examine the effectiveness of these interventions in improving the health of women. METHODS: Eight electronic databases will be searched to identify all prospective cohort and experimental studies examining the impact of e-health interventions for increasing MVPA levels among working-age women (mean age 18-65 years) in developed countries. Gray literature including theses, dissertations, and government reports will also be examined. Study quality will be assessed using a modified Downs and Black checklist, and risk of bias will be assessed within and across all included studies using the Cochrane's risk of bias tool and Grades of Recommendation, Assessment, Development and Evaluation approach. A quantitative synthesis in the form of meta-analyses for measures of MVPA and health outcomes will be conducted where possible. DISCUSSION: This review will determine the effectiveness of e-health interventions in raising MVPA levels in working-age women in developed countries. It will form a contemporary, rigorously developed, and reliable research base for policy makers and stakeholders; and inform and influence the development and implementation of effective e-health interventions designed to increase MVPA levels and improve health outcomes in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009534.

Coffee and cholesterol in epidemiological and experimental studies.

Twenty-two cross-sectional studies involving 130,000 persons from 8 different countries have reported their findings on the association between coffee consumption and cholesterol levels. Results of these reports display a variety of trends in the association between coffee intake and serum cholesterol concentrations: 8 (36%) studies demonstrated a significant positive association in both sexes, and 5 (23%) studies showed no association in men or women. In 3 other reports where both sexes were included, significant positive association was observed only in women. The remaining 6 investigations examined only men with 4 (18%) reporting a significant correlation between coffee and cholesterol. This unexplained incongruity of cross-sectional data points to a relationship between coffee and cholesterol in some populations, which needs to be further explored. In addition, HDL cholesterol levels appeared unrelated to coffee intake in the 11 studies in which it was measured. The 7 available human experiments showed the same low level of agreement in the results among small numbers of volunteers. Experiments involving different brewing methods suggest that a major part of the cholesterol-increasing effect can be explained by different brewing methods. A critical assessment of the published reports leads to the conclusion that the data are insufficient to warrant public health admonitions against coffee drinking, but that it may be of clinical importance in some hypercholesterolemic individuals.