Evangelia Kaklamani

Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma

During a 4‐year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti‐HCV) by third‐generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose‐response, positive association between smoking and HCC risk [≥ 2 packs per day, odds ratio (OR)=2.5].This association was stronger in individuals without chronic infection with either HBV or HCV (≥ 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super‐multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti‐HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together. Int. J. Cancer 85:498–502, 2000.

Dietary Fat and Carbohydrates Are Independently Associated With Circulating Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor–Binding Protein 3 Concentrations in Healthy Adults

PURPOSE To evaluate and quantify the association between consumption of specific food groups/macronutrients and concentrations of serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3). SUBJECTS AND METHODS Data from a comprehensive food-frequency questionnaire administered to 115 healthy subjects were used to study cross-sectionally the relationship between nutritional factors and circulating IGF-1 and IGFBP-3 concentrations. Adjustment for the effect of total energy intake and a series of epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol consumption, and coffee drinking) was implemented through multivariate linear regression. RESULTS We observed that serum levels of IGF-1 are positively associated with consumption of red meats, fats, and oils. In addition, serum levels of IGF-1 are independently and positively associated with energy intake from lipids and negatively associated with energy intake from carbohydrates. Finally, serum levels of IGFBP-3 are independently and negatively associated with energy intake from saturated fat. CONCLUSION Serum IGF-1 and/or IGFBP-3 concentrations are associated with red meat, carbohydrate intake, and fat intake and, thus, may mediate the effect of these dietary factors on the pathogenesis of several disease states. Additional studies are needed to further quantify these associations and elucidate the underlying mechanisms.

Age, sex, and smoking are predictors of circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3

PURPOSE Insulin-like growth factor (IGF-1) and its major binding protein (IGF-BP3) have recently been implicated in the pathogenesis of several malignancies. However, anthropometric and lifestyle predictors of these hormones have not been elucidated. Here we report the results of a cross-sectional study. SUBJECTS AND METHODS This cross-sectional study examines the relationship of a series of epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol consumption, and coffee drinking) with IGF-1 and IGF-BP3 in a sample of 130 healthy adults. RESULTS We observed that serum levels of IGF-1 are higher, whereas levels of IGF-BP3 are lower, in men than in women. In addition, serum levels of IGF-1 are independently and negatively associated with age and positively associated with pack-year history of smoking. Finally, serum levels of IGF-BP3 are independently and negatively associated with the number of cigarettes smoked per day or pack-year history of smoking. CONCLUSION Age, sex, and smoking are independent predictors of IGF-1 and/or IGF-BP3. The influence of these epidemiologic variables on the pathogenesis of disease states associated with IGF-1 and IGF-BP3 warrants further exploration.

Adamantiades-Behçet’s disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells

Abstract The serum levels of several cytokines were determined in 94 patients with Adamantiades-Behçet’s disease (ABD), aged 36.1 ± 11.0 years, during the active stage ( n = 75) and the inactive stage ( n = 19) of the disease. A group of 75 healthy individuals matched for age and sex served as controls. Cytokine levels were determined using commercially available ELISA kits. Of the 75 patients with active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively, and 23 healthy controls (31%) were found to have detectable levels of interleukin 8 (IL-8) in their serum ( P < 0.05). Also, increased IL-8 serum levels were found in patients with active disease (median 12 pg/ml, P = 0.010) compared to patients with inactive disease (≤ 10 pg/ml) and to healthy controls (≤ 10 pg/ml). In particular, patients with oral aphthous ulcers ( n = 51, 34 pg/ml) and neurological features ( n = 4, 71 pg/ml) exhibited increased IL-8 levels. In contrast, there was no correlation between disease activity and the serum levels of IL-1α, IL-1β, tumor necrosis factor alpha (TNF-α), soluble intercellular adhesion molecule-1 or basic fibroblast growth factor (bFGF). In a second set of experiments, the involvement of dermal microvascular endothelial cells in IL-8 secretion was investigated. Immortalized human dermal microvascular endothelial cells (HMEC-1 cells) were maintained for 4 h in vitro with serum from 18 ABD patients or with IL-1β, a known stimulator of IL-8 synthesis, TNF-α or their combination at five- to tenfold higher concentrations than those found in the serum of ABD patients. Increased IL-8 secretion was found after incubation with ABD patients’ serum (median 20 pg/ml), but IL-1β TNF-α and IL-1β + TNF-α failed to induce IL-8 secretion by HMEC-1 cells (≤ 1–1.2 pg/ml) in biologically relevant concentrations. Our study showed increased IL-8 serum levels in ABD patients with active oral and neurological manifestations. Human microvascular endothelial cells may, at least partially, be responsible for the enhanced IL-8 secretion in the active stage of the disease.

Hepatitis B and C viruses in the etiology of hepatocellular carcinoma; a study in Greece using third-generation assays

AbstractObjectives: The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC). Methods: During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays. Results: The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5–78.3) for the presence of HBsAg and 23.2 (11.4–47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9–216.6) compared to infection with neither virus. Conclusions: Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses.

HLA-B∗5101 in Greek Patients with Behçet’s Disease

Behçets disease (BD) is a recurrent systemic vasculitis of unknown etiology. Genetic factors and infectious agents seem to be related to the etiology and pathogenesis of the disease. BD is strongly associated with HLA-B51 antigen in many ethnic groups. As there are differences in HLA profile in different ethnic groups, we designed this case-control study to examine the association of HLA-B51 alleles and BD as well as to investigate the influence of sex, age at development of the International Study Group (ISG) for Behçets Disease criteria and certain features of disease severity on the strength of this association. The study includes 62 Greek BD patients who fulfill the ISG criteria for Behçets disease and 87 controls. Serological HLA Class-I typing was performed by standard microlymphocytotoxicity technique. HLA-DNA typing for the B5 group was performed in all B51 subjects and controls by PCR-SSO. Allele B*5101 was found in 80% of BD patients and in 26% of controls (odds ratio (OR) 10.48, p < 10[-6]). Males who carry this allele have a higher risk than females for BD (OR 16.97 and 5.74 respectively). B*5101 predisposes to BD at a younger age in both sexes and to the development of erythema nodosum (OR = 11, p = 0.004). This was confirmed by multiple logistic regression analysis. A weak but not significant association was found between B*5101 and uveitis (OR = 2). No association was found between B*5101 and vasculitis or skin lesions in either sex. It was concluded that in the Greek population allele B*5101 is a predisposing marker for BD, as in most ethnic groups, and that this allele predisposes to the development of the disease at a younger age in both sexes and to the development of erythema nodosum.

Enhanced phagocytosis of mononuclear phagocytes in pregnancy

The phagocytic activity of peripheral blood mononuclear phagocytes for Staphylococcus epidermis of healthy non-pregnant and pregnant women throughout pregnancy was examined in relation to gestational age. The study included 30 healthy non-pregnant women and 90 healthy pregnant women equally distributed across the three trimesters. Two variables were investigated: the number of mononuclear cells in phagocytosis and the average number of bacteria per monocyte in phagocytosis. As pregnancy progressed a gradual and significant increase was found in the number of monocytes in phagocytosis and a significantly higher proportion of macrophages with six or more bacteria per phagocyte.

Autoantibodies in systemic lupus erythematosus and normal subjects

SummaryThe presence of various antibodies in serum samples from patients with systemic lupus erythematosus (SLE) and from healthy subjects was investigated by ELISA, using a panel of natural antigens. Fifty-eight serum samples from 58 healthy women and 50 serum samples from 30 patients with active SLE were tested with 9 natural antigens (ds-DNA, actin, tubulin, thyroglobulin, myosin, myoglobin, human transferrin, human interferon a and BSA FV). It was found that the proportion of positive sera from healthy women at a dilution of 1/20 was almost the same as that of lupus sera at a dilution of 1/150 for nearly all antigens, while at a dilution of 1/150 the proportion of positive sera from patients with SLE was significantly higher for nearly all antigens. In lupus sera a high degree of correlation was observed between titers of anti-DNA and titers of the other antibodies. One hundred eighty-eight serum samples from 53 SLE patients, taken during exacerbation and remission of the disease were tested with ds-DNA, actin and tubulin. Antibodies (IgG) to ds-DNA actin and tubulin were found in the majority of serum samples taken during the active phase of the disease. On the other hand, very few serum samples taken during remission were found to be positive. A high degree of correlation was found between the OD of anti-actin/anti-ds-DNA (r=0.769) and anti-tubulin/anti-ds-DNA (r=0.829). In a competitive enzyme immunoassay for DNA, actin, tubulin, myosin and thyroglobulin, a high degree of inhibition was observed with the homologous antigens. Cross inhibition was observed between actin, tubulin and myosin, and to a lesser degree with DNA. These results indicate that normal sera contain low titers of auto and foreign antibodies while active SLE sera react strongly with the same antigens.

Hashish smoking and T-lymphocytes

To investigate the effect of long term hashish use on T-lymphocytes we have measured the incorporation of14C-thymidine by peripheral blood lymphocytes, unstimulated and stimulated by phytohemagglutinin, as well as the proportion and number of E-rosettes in 12 healthy male chronic users of the drug before and after a smoking session, and in 15 control subjects.The results show that hashish smoking does not impair the response of lymphocytes to PHA, at least at the concentration of PHA used. Furthermore there is a possibility that among chronic users a hashish smoking session may have a slight stimulatory effect.ZusammenfassungZur Untersuchung des Langzeiteffekts von Haschischgebrauch auf T-Lymphozyten haben wir den Einbau von14C-Thymidin in Lymphozyten des strömenden Blutes ohne und mit Stimulierung durch Phythämagglutinine (PHA) gemessen. Zugleich wurde das Zahlenverhältnis von E-Rosetten bei zwölf gesunden männlichen chronischen Haschischkonsumenten vor und nach einer Rauchperiode bestimmt sowie mit 15 Kontrollpersonen verglichen. Haschischrauchen ergab keine Schädigung der Lymphozytenrekation auf PHA, wenigstens bei der verwendeten PHA-Konzentration. Es ist nicht ausgeschlossen, daß nach chronischem Haschischrauchen eine leichte Stimulierung eintritt.

Hepatitis B serology in Greek prostitutes: significance of the different serum markers.

One hundred and ninety-eight prostitutes (mean age 41.8 years) and 117 control women of low socio-economic class (mean age 43.8 years) were tested by solid-phase radioimmunoassay for hepatitis B surface antigen (HBsAg), its antibody (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). The prevalence of HBsAg was higher among prostitutes (11% v. 4%, P approximately 0.06). This difference was accounted for by the higher infection rate of prostitutes to hepatitis B virus (HBV) 97% v. 45%, P less than 10(-6)), since the proportion of HBsAg carriers among those infected was practically the same between the two groups (11% v. 9%). Among the previously infected prostitutes who did not become carriers the majority (75%) were positive for both anti-HBc and anti-HBs, whereas among control women about half (52%) were positive only for anti-HBc.