Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Epidemiologic risk factors for incident sexually transmitted diseases in young Thai men.

BACKGROUND AND OBJECTIVES: Prospective studies of incidental sexually transmitted diseases in developing countries rarely have been reported. As the human immunodeficiency virus epidemic widens, knowledge of the epidemiology of sexually transmitted diseases as co-factors for human immunodeficiency virus infection is viewed as vitally important. GOAL: To determine epidemiologic risk factors for incidental sexually transmitted diseases in young men in northern Thailand. STUDY DESIGN: A cohort of 2,417 men selected by lottery for military conscription was followed an average of 22 months, with epidemiologic risk factors and sexually transmitted disease histories assessed semiannually. Sexually transmitted diseases were determined by physician or symptom histories obtained by interview. RESULTS: Sexually transmitted disease incidence was 17.04 per 100 person-years. Gonorrhea and chancroid were commonly reported, whereas incident syphilis was rare. Sexually transmitted disease incidence declined significantly in the 2-year period. Most sexually transmitted diseases were acquired through commercial sex patronage. However, among men who did not report visiting a brothel, there was a significant increase in sexually transmitted diseases among men reporting sex with a girlfriend. Other risk factors included inconsistent condom use, drug use, and low educational level. Frequent alcohol use was associated with incident sexually transmitted diseases in bivariate analysis, but drinking at the time of last brothel visit was not associated with increased sexually transmitted diseases. CONCLUSIONS: Sexually transmitted disease control in Thailand is based on an integrated sexually transmitted disease clinic system. Many commercial sex workers are examined and treated routinely, but too infrequently to reduce sexually transmitted disease transmission between them and their male clients. Condom-use levels in commercial sex settings still may be too low to reduce sexually transmitted disease transmission. More consistent and effective sexually transmitted disease treatment of commercial sex workers and their clients and education of men on the effective and consistent use of condoms is required to reduce the risks of sexually transmitted disease transmission in this population.

PIP: A cohort of 2417 male military conscripts had their epidemiologic risk factors for exposure to sexual transmitted diseases (STD) and STD histories assessed semiannually for an average of 22 months. STDs were determined by physician or symptom histories obtained during interview. These measures were undertaken to determine the epidemiologic risk factors for incidental STDs in young men in northern Thailand. The incidence of STD was 17.04 per 100 person-years. Gonorrhea and chancroid were commonly reported, while it was rare to see syphilis. The incidence of STD declined significantly during the two-year period. Most STDs were acquired through having sex with prostitutes. However, among men who did not report visiting a brothel, there was a significant increase in STDs among men reporting having sex with their girlfriends. Other risk factors included inconsistent condom use, drug use, and low educational level. Frequent alcohol use was associated with incident STDs in bivariate analysis, but drinking at the time of last brothel visit was not associated with increased STDs.

Dynamics of risk behavior for HIV infection among young Thai men.

The objective of this investigation was to analyze the dynamics of risk for HIV-1 infection among young men in Thailand. We conducted a prospective study in a cohort (n = 1,236) of young men, aged 19-23 years at conscription into the Royal Thai Army and Air Force from six provinces in northern Thailand in May 1991 who were followed until their discharge in April 1993. The outcome measure was change since conscription in the frequency of self-reported sex with female commercial sex workers (CSW) during military service. Although 42% of conscripts reported no visit to a female CSW in the year prior to conscription, most had a visit during military service. Men who visited female CSWs infrequently at baseline increased their visits somewhat over time, whereas those with high initial rates of CSW visits decreased. Based on an assumed stable distribution over time, change from baseline was not statistically significant. Only marital status and high baseline CSW visit rates were associated with diminished visit frequency in multivariate analysis. No differences were seen in patterns of change in CSW visits by HIV-1 serostatus. More aggressive preventive interventions are needed to reduce the frequency of CSW visits in northern Thailand, a setting where 40-80% of all female CSWs working in brothels are now HIV seropositive.

Epidemiologic characteristics of leprosy reactions.

An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification.

Seroprevalence of HIV antibodies and risk factors in healthy young males from upper north Thailand.

In the Spring of 1991 a random sample of young men from Upper Northern Thailand (mean age = 21 years) was interviewed by trained medical students from Chiang Mai University, serum samples were obtained and analyzed for prevalence of HIV-1 antibodies and for syphilis, and risk factors for HIV infection were assessed. It was found that Commercial Sex Workers (CSW) were the principal risk factor, that consistent condom use is rare, and the rates of HIV infection are rising rapidly. Sociodemographic background, homosexual behavior, drug use, and history of STD's were found to be not significant risk factors. The conclusions are that the education campaigns should be intensified to reduce the frequency of contact with CSW and to encourage consistent use of condoms.

HIV-1 infection among lower class commercial sex workers in Chiang Mai, Thailand.

OBJECTIVE: To determine risk factors for HIV-1 infection in female commercial sex workers (CSW) in northern Thailand. METHODS: A cross-sectional survey of female CSW from 11 sex establishments frequented by military conscripts that included an interview and serological testing for HIV-1. RESULTS: The HIV-1 seroprevalence in 230 CSW was 65%; the rate was lower among CSW from Chiang Mai than from rural areas. Multivariate logistic regression analysis for HIV-1 included the following significant factors: non-urban location of the sex establishment, ethnic Thai lowlander, lower price, history of genital warts and dysuria. Condom use, number of partners and duration of employment were not significantly associated with HIV-1 prevalence after adjustment for other risk factors. CONCLUSIONS: The high level of HIV-1 seroprevalence in this sample demonstrates the risk of transmission in lower cost commercial sex encounters in northern Thailand. Non-Thais (ethnic Hill tribes and Burmese) had lower HIV-1 prevalence than ethnic Thais. Type of establishment ('direct' brothel-based or 'indirect' establishments) was not predictive of HIV-1 seroprevalence. However, rural establishments were less vigilant in promoting condom use, suggesting the need for renewed efforts to enforce the Ministry of Public Health's '100% Condom Campaign' in commercial sex establishments.

Cholinesterase activity in the chondrocranium of normal and exencephalic mouse fetus with trisomy 12.

Cholinesterase (ChE) activity in the chondrocranium of normal and exencephalic trisomy 12 mouse fetuses was studied. Non-specific cholinesterase activity was found strongly in the developing bone cells at the central zone and weakly in the more maturely developed bone cells at the peripheral zone of the chondrocranium of both normal and exencephalic trisomy 12 mouse fetuses. In exencephalic mouse fetuses, the ChE-activity was lesser than in the normal ones which corresponded to hypoplastic chondrocranium. The centrifugal direction of the maturity of individual bone cells could be demonstrated by the activity of cholinesterase. The young bone cells showed strong ChE-activity while the more matured cells showed weak ChE-activity. The enzyme activity disappeared when the definite tissue structure was well developed. From this study, it may be concluded that ChE plays a role in chondrocranium development which is different from its known function in the adult tissue.

Studies of human leprosy lesions in situ using suction-induced blisters: cell changes with IgM antibody to PGL-1 and interleukin-2 receptor in clinical subgroups of erythema nodosum leprosum.

To examine the immunopathogenesis of type 2 erythema nodosum leprosum (ENL) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 57 patients with reactions (19 acute ENL and 38 chronic ENL), 61 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells, IgM antibody to PGL-1 and Tac peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During ENL reactions: a) the lesions in chronic ENL showed a decreased number of CD8+ (T-suppressor) cells and increased helper/suppressor ratio as compared to those in acute ENL and non-reactional leprosy; b) Tac peptide and IgM antibody to PGL-1 levels were elevated in the chronic ENL lesions; c) and systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population and IgM antibody to PGL-1 but did not change CD8+ cell population and the levels of Tac peptide in the lesions. The elevated levels of Tac peptide were localized in the skin lesions while increased levels of IgM anti-PGL-1 seemed to be filtered from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of decreased CD8+ and relatively increased CD4+ cells, are important features of chronic, recurrent ENL reactions and may be an intermittent or cyclic phenomenon during the reaction. Understanding the mechanisms of these spontaneous changes in immunity in leprosy will enlarge our knowledge of reactions and of the underlying determinants of delayed type hypersensitivity and cell-mediated immunity in leprosy, which in turn will allow us to realize the potential for artificially manipulating these responses as proposed with vaccines or immunotherapy.

Studies of human leprosy lesions in situ using suction-induced blisters. 2. Cell changes and soluble interleukin 2 receptor (Tac peptide) in reversal reactions.

To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 10 patients with reactions, 24 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells and Tac-peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During reversal reactions: a) the lesions contained an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide levels were elevated in half of the lesions; c) the increases in Tac peptide and CD4+ cells were directly correlated; and d) systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population. These findings were localized to the skin, and do not represent simple filtration of these components from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an important feature of reversal reactions, and may be an intermittent or cyclic phenomenon during the reaction. Findings in active patients without reactions are consistent with the hypothesis that differing states of immunologic equilibrium have been established in different portions of the leprosy spectrum. In reversal reactions we may, therefore, be examining immunologic processes set in motion when a pre-existing equilibrium has been upset by spontaneous, natural events. The mechanism of such spontaneous changes in immunity in leprosy is of considerable interest, not only to understand the reaction, but also to examine the underlying determinants of delayed-type hypersensitivity and cell-mediated immunity in leprosy and the potential for artificially manipulating these responses, as proposed with vaccines or immunotherapy.

Cell changes and soluble interleukin-2 receptors (Tac peptide) in leprosy reversal reactions using suction-induced blisters.

The cellular contents and soluble interleukin-2 receptor (IL-2R) [Tac peptide] of skin blisters induced by suction over 7 reversal reaction (RR) patients were examined using immunoperoxidase and ELISA techniques respectively. The helper T activity (CD4+ cells) and helper:suppressor ratio were significantly greater in borderline lepromatous (BL) lesions with RR than in quiescent BL lesions. Interestingly, the intracutaneous levels of Tac peptide were elevated and directly correlated with the increases in CD4+ cells. The systemic administration of corticosteroids revealed a reduction in the numbers of CD4+ cells in the lesions. These results indicate that RRs are manifestations of a spontaneous increase in delayed type hypersensitivity (DTH) and possibly cell mediated immunity (CMI) in leprosy patients. The mechanism of such changes in immunity is of considerable value in understanding reversal reactions and the underlying determinants of DTH and CMI in leprosy and this in turn will have a bearing on the potential for proposed vaccines or immunotherapy.

Epidermal carcinoma: a five year (1981-1985) pathological analysis at Chiang Mai University Hospital.

A total of 414 cases of epidermal carcinoma registered at the Department of Pathology, Faculty of Medicine, Chiang Mai University during the years 1981 to 1985 were analysed in detail. The disease was more prevalent in males than in females. The incidence was 55.56 per cent in males and 44.44 per cent in females. At the age interval between 50 to 79, epidermal cancers were most frequently seen. Most of the patients were farmers. The patients usually came to the hospital with signs and symptoms of mass and ulcer. The histological cell types were squamous cell carcinoma (50.25%), basal cell carcinoma (34.54%), malignant melanoma (14.01%) and other (1.21%). The etiology of epidermal carcinoma is not definitely known, therefore, the possible epidemiologic etiology was briefly discussed.

Oral cancer in northern Thailand.

Statistical material accumulated at the Faculty of Medicine, Chiang Mai University, Thailand, revealed that oral cancer ranked third in both sexes during 1975-1984 and 1981 alone. In 1987 oral cancer had dropped to rank 7 of cancers of all sites. Since there is evidence of disappearance of traditional chewing and smoking habits in Northern Thailand this may result in changing incidence of oral cancer in this province.

Studies of human leprosy lesions in situ using suction-induced blisters. 1. Cellular components of new, uncomplicated lesions.

The cellular contents of blisters induced by suction over new, uncomplicated leprosy lesions, and in the skin of cured, control patients, have been examined with enzyme- and immuno-histochemical staining over a period of 4 days. The total cellularity of the blisters varied over a wide range, not correlated with the type of leprosy. Mononuclear cells predominated at all times studied, with nearly equal percentages of monocytes and T lymphocytes. The T-helper: suppressor ratio was significantly greater in BT than in BL and LL lesions at 48 hr. Suction blisters offer a painless, quantitative, reproducible, multiple-sampling method for obtaining cells from the cutaneous infiltrates of leprosy for phenotyping or functional analysis.

Precancerous and other oral mucosal lesions related to chewing, smoking and drinking habits in Thailand.

In a field study (1979-1984) four out of six major hilltribes of Northern Thailand, namely the Lahu, Karen, Lisu and Meo, as well as a group of rural Thai, were examined. Chewing, smoking and drinking habits and lesions of the oral mucosa (leukoedema, preleukoplakia, leukoplakia and chewer's mucosa) were recorded. 1866 individuals were examined. Considerable differences in the chewing and smoking habits among the various tribes were recorded and some of them were considered tribe-specific. Chewing of betel and miang was more prevalent among older people; these habits seem to have lost their attraction for the younger people. Cigarette smoking was more prevalent among middle-aged individuals. Leukoedema was observed in 12.4%, preleukoplakia in 1.8%, leukoplakia in 1.1% and chewer's mucosa in 13.1%. Men and the older generation were affected more often, except that more women (Karen and Thai) revealed chewer's mucosa. A positive correlation could be demonstrated between some mucosal lesions (leukoedema, chewer's mucosa) and some smoking and chewing habits.

Ultrastructural findings in the oral mucosa of betel chewers.

Eighteen biopsies of the oral mucosa of northern Thai hilltribe betel chewers were studied histologically and by transmission and scanning electron microscopy (TEM, SEM). Clinically, varying stages of epithelial atrophy and one case of submucous fibrosis were observed. Histologically, epithelial atrophy with marked reduction of the rete pegs, hyperortho- and/or parakeratosis, and subepithelial edema and inflammatory changes were the prominent findings. On the ultrastructural level, cytoplasmic projections of the basal cells into the subepithelial stroma were seen. The basal membrane frequently revealed gaps; the interepithelial space was widened and unusual microvilli were observed on cell surfaces (SEM). Intercellularly, cristalloid material of unknown origin was also seen. The subepithelial connective tissue was characterized by dense bundles of collagen fibres adjacent to which masses of amorphous material were located. While some of the ultrastructural findings in the epithelium of betel chewers are indicative of early dysplastic changes, the nature of the juxta-epithelial stromal alterations is still unknown. Current hypotheses regarding the etiology of oral submucous fibrosis are briefly discussed.