Iron-binding proteins and risk of cancer in Taiwan.

The relationship of serum ferritin and transferrin levels to risk of cancer was examined in a population of 21,513 Chinese male government workers in Taiwan who have been followed prospectively since 1975. On the basis of a previous study in the Solomon Islands, increased ferritin and decreased transferrin levels were predicted for those men who developed cancer. The results were consistent with the prediction. The mean serum ferritin was higher at the start of the study in 192 men who had died of cancer or who had developed primary hepatocellular carcinoma (PHC) as of July 1983, as compared to their controls. The mean serum transferrin level was lower in men who had died of cancers other than PHC. The estimate of relative risk of cancer death for a man with 200 ng ferritin/ml and 200 mg transferrin/dl, as compared to a man with levels of 20 ng/ml and 400 mg/dl, respectively, is 2.9. These serum iron-binding protein levels are at the extremes of the "normal" range. Men who subsequently died of cancer had lower hemoglobin, lower hematocrit, lower albumin, and higher globulin levels at the start of the study than did the controls. These results are consistent with the hypothesis that increased iron stores increase the risk of cancer. However, direct assessment of iron stores prior to disease was not possible, and the same constellation of findings may be consistent with other explanations.

Yield of chest radiograph in tuberculosis screening for HIV-infected persons at a district-level HIV clinic.

SETTING: An Hoa Clinic, a district-level human immunodeficiency virus (HIV) clinic in Ho Chi Minh City, Viet Nam. OBJECTIVE: To assess the performance of chest radiograph (CXR) in screening for pulmonary tuberculosis (PTB) among HIV-infected individuals and identify misdiagnosed opportunities. DESIGN: This cross-sectional study was conducted in 397 HIV-infected patients consecutively enrolled at the An Hoa Clinic in Ho Chi Minh City, Viet Nam, from August 2009 to June 2010. The performance of CXR in TB screening was assessed based on its sensitivity, specificity, positive likelihood ratio and negative likelihood ratio. RESULTS: Symptom screening alone missed 50% of PTB cases. The combination of CXR and symptom screening yielded an additional 28.6% (8/28) in PTB screening as compared with symptom screening alone, and should be applied routinely, especially in high TB prevalent settings. CONCLUSION: CXR is a good predictor for PTB even in HIV-infected individuals. The combination of CXR and screening for common TB symptoms considerably improved the sensitivity of detecting active PTB in people living with HIV. If available, routine sputum culture and the World Health Organization-endorsed Xpert(®) MTB/RIF assay should be implemented to achieve a more accurate diagnosis.

Mutagen sensitivity as a susceptibility marker for human hepatocellular carcinoma.

Although the pathogenesis of hepatocellular carcinoma (HCC) remains poorly understood, hepatitis B virus and dietary aflatoxin exposures are established etiological factors for this disease. We conducted a pilot study of 28 patients with HCC and 110 healthy controls matched for age, sex, and ethnicity to determine whether constitutional genetic instability, based on the quantification of mutagen-induced chromatid breaks in cultured lymphocytes, modifies an individual's risk of HCC development. The mean numbers of bleomycin-induced breaks per cell for cases and controls were 0.92 and 0.55, respectively (P < 0.0001). For benzo(a)pyrene diol epoxide (BPDE) sensitivity, the values were 0.90 for cases and 0.46 for controls (P < 0.0001). Nearly 68% of the cases but only 27% of the controls exhibited bleomycin sensitivity (i.e., had > or = 0.68 breaks per cell). Eighty % of the case group but only 22% of the control group exhibited BPDE sensitivity (i.e., had > or = 0.58 breaks per cell). On multivariate analyses, both bleomycin sensitivity and BPDE sensitivity were associated with significantly elevated risks for HCC, with odds ratios (95% confidence intervals) of 5.63 (2.30, 13.81) and 14.13 (3.52, 56.68), respectively. For individuals who were sensitive to both assays, the risk was 35.88. A synergistic interaction between the bleomycin sensitivity and BPDE sensitivity in HCC risk was suggested. These preliminary findings suggest that differences in host factors related to the predisposition to chromosome breakage, the capacity for DNA repair, or both may be involved in HCC development by influencing the predisposition of hepatitis B virus integration into human DNA or that the carcinogens induced DNA damage susceptibility. A larger study is needed to confirm these intriguing results.

Reduced expression of mismatch repair genes in colorectal cancer patients in Egypt.

An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.

Excess mortality and influenza surveillance in Taiwan.

Excess mortality has proven to be a useful epidemiologic tool for influenza surveillance in the temperate zone. A retrospective analysis of the epidemiology of influenza in Taiwan was undertaken to explore the usefulness of this technique in the tropical--subtropical zone. Excess mortality similar to that observed during influenza epidemics in the temperate zone was noted during periods of previously recognized influenza epidemics in Taiwan. For the very young and the elderly excess mortality was observed to be even higher than in the temperate zone. Virus isolations, increased school absenteeism, and high clinical attack rates were also noted during influenza epidemics. Use of these epidemiologic techniques in Taiwan proved to be a useful approach to describe the impact of influenza.

Surgical treatment of 109 patients with symptomatic and asymptomatic hepatocellular carcinoma.

A total of 109 patients with histologically proved hepatocellular carcinoma (HCC) have undergone hepatic resection during the 56-month period from October 1978 to May 1983. There were two sources of patients: those with symptomatic HCC (n = 47) and those with asymptomatic HCC (n = 62). A family tendency of HCC was noted in 11% of the patients studied. The percent of positive hepatitis B surface antigen (HBsAg) was 87%, and the serum alpha-fetoprotein was less than 20 ng/ml in 30% in the group with symptoms. The operative mortality rate was 3% and the hospital mortality rate was also 3%. The postoperative course was complicated with pleural effusion in 10%, bile leakage in 4%, subphrenic abscess in 4%, and upper gastrointestinal bleeding caused by gastritis in 1% of the patients. The actual survival rate for the 103 cases was 84% for 350 days and 28% for 1400 days. However, in the group with asymptomatic HCC with an average tumor size of 3.35 +/- 1.49 cm in diameter, the rate was 92% for 350 days and 44% for 1400 days. In the group with symptomatic HCC with an average tumor size of 10.6 +/- 5.1 cm in diameter, the rate was 76% for 350 days and 8% for 1400 days. The survival rate of the group with asymptomatic HCC was far better than that of the group with symptoms (p less than 0.05). In analysis of factors that might affect the patient's survival, only second or third operations (p less than 0.05), typical gross findings of tumor appearance (p less than 0.05), and an adequate margin were closely related (p less than 0.001). Neither the tumor size, the status of accompanying liver cirrhosis, the tumor location, nor the patient's sex and age affected the patient's survival (all p greater than 0.05).

HBsAG and HBeAG markers among pregnant women in Manila, Philippines.

The sera of 5,684 pregnant women were tested for HBsAG and 432 (7.6%) were found positive. Positive HBsAG sera were then tested for the e antigen and of 413 tested, 115 or 27.8% were positive. The over-all prevalence rate of e antigen was 2.03%. All women were asymptomatic. Six of 13 HBsAG-HBeAg-positive mothers delivered infants who became HBsAg-positive within two years of age for a rate of 46%. The findings support earlier studies on the importance of the e antigen as an index of perinatal transmission. Also, they support evidence of unusually high rates of transmission among Asian ethnic groups.

Low prevalence of rheumatoid arthritis in Chinese. Prevalence survey in a rural community.

A prevalence survey for arthritis among the general adult population of a rural island off the coast of China revealed a prevalence of rheumatoid arthritis (RA) of no more than 0.3% compared with 1.0% among Americans in the National Health Examination Survey (NHES). The frequency of clinical ankylosing spondylitis (AS) (0.2%) appears to be higher than expected, although limited data are available for comparison. No clinically unusual features of these diseases were recognized.

Association between smoking and size of anal warts in HIV-infected women.

While the association between smoking and human papillomavirus infection, cervical cancer, and anal cancer has been well studied, evidence on the association between cigarette smoking and anal warts is limited. The purpose of this study was to investigate if cigarette smoking status influences the size of anal warts over time in HIV-infected women in a sample of 976 HIV-infected women from the Women's Interagency HIV Study (WIHS). A linear mixed model was used to determine the effect of smoking on anal wart size. Even though women who were currently smokers had larger anal warts at baseline and slower growth rate of anal wart size after each visit than women who were not current smokers, there was no association between size of anal wart and current smoking status over time. Further studies on the role of smoking and interaction between smoking and other risk factors, however, should be explored.

Improving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet Nam.

SETTING: District 6, An Hoa Clinic in Ho Chi Minh City (HCMC), Viet Nam. OBJECTIVE: To evaluate the performance of various algorithms in tuberculosis (TB) screening and diagnosis in a human immunodeficiency virus (HIV) infected population in HCMC, Viet Nam. DESIGN: A cross-sectional study of 397 consecutive HIV-infected patients seeking care at the An Hoa Clinic from August 2009 to June 2010. Data on participant demographics, clinical status, chest radiography (CXR) and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and pulmonary TB (PTB). RESULTS: The prevalence of sputum culture-confirmed PTB, acid-fast bacilli (AFB) positive TB, and multidrugresistant TB among the 397 HIV-infected patients was respectively 7%, 2%, and 0.3%. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were respectively 3.17, 32.04 and 4.28. Clinical findings alone had poor sensitivity, but combining CD4+ cell count, AFB sputum smear and CXR had a more accurate diagnostic performance. CONCLUSION: Results suggest that symptom screening had poor clinical performance, and support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Viet Nam. However, when routine sputum culture is not available, an algorithm combining CD4+ cell count, AFB sputum smear and CXR is recommended for diagnosing PTB.

Postnatal infectivity of hepatitis B surface antigen-carrier mothers.

The incidence of hepatitis B virus (HBV) infections during the second and third year of life was determined for 105 children whose mothers were carriers of hepatitis B surface antigen. Children were given hepatitis B immune globulin (HBIG) at birth and in some instances three and six months later to protect against HBV infection. Passive antibodies from the dose of HBIG disappeared in three to four months. Infants negative for HBV markers at 12 months were selected and subsequent infections were analyzed in relation to the e system markers in the mother. Over an average of 17.5 months of follow-up, 38.1% of the infants became infected, an annual incidence rate of 26.0%. The rate was highest for children whose mothers were positive for hepatitis B e antigen (HBeAg) (57.1%), moderate for those whose mothers were negative for both HBeAg and antibody to HBeAg (anti-HBe) (20.4%), and lowest for those whose mothers were positive for anti-HBe (11.3%).

Immunogenicity of hepatitis B virus vaccine (Heptavax-B)--response of healthy adults.

We vaccinated 30 healthy adults who were susceptible to hepatitis B virus with 20 mug of Merck Sharp & Dohme vaccine at zero, one and six months and measured their antibody (anti-HBs) response weekly for four weeks and monthly for at least seven months. A month following the first dose 40% had antibodies and 90% were positive for anti-HBs a month following the second dose. The third dose raised the response rate to 93.3% but its major effect was to substantially raise the titer of virtually all of the vaccinees. Two persons had no antibody response to vaccination and four others were hyporesponders. No complications or significant side effects were observed.

HBeAg and anti-HBe detection by radioimmunoassay: correlation with vertical transmission of hepatitis B virus in Taiwan.

A sensitive radioimmunoassay technique was used to detect hepatitis B e antigen (HBeAg). A strong correlation was found between HBeAg positivity of the serum of hepatitis B surface antigen (HBsAg) carrier women in Taiwan and the subsequent development of surface antigenemia in their babies. All babies who became chronic HBsAg carriers were born to HBeAg positive women, maternal HBeAg positivity being a better prior indication of chronic antigenemia developing in the baby than the HBsAg titer in the mother's serum.

Epidemiology of hepatitis B virus infection in South African Chinese.

The authors determined the age-specific prevalence of hepatitis B virus markers in 1,408 Chinese who resided in South Africa in 1983-1985. The small South African Chinese community consists of original Chinese settlers, almost all of whom migrated from the hepatitis B virus endemic mainland China province of Guangdong, and their South African-born descendants. The Chinese live among the white South African community, which has a very low hepatitis B virus carrier rate. The overall hepatitis B virus carrier rate was 5.3%, and the carrier rate was highest in age group 30-39 years (11.9%) and significantly lower in children aged 1-9 and 10-19 years (2.4% and 2.0%, respectively). Overall infection rates increased progressively with increasing age, starting at about 10% in the children aged 1-19 years and reaching 50% in adults aged 60-69 years. Among carrier children, 89% had carrier mothers, and all of the latter were also hepatitis e antigen (HBeAg)-positive. The prevalence of hepatitis B virus carriers in South African Chinese women of child-bearing age was 6.1%, and 41.9% of these carriers were HBeAg-positive. The age-specific prevalence of hepatitis B virus markers among South African Chinese is appreciably lower than that of Chinese in southeastern China, who have carrier rates of 15-20% with a peak in childhood. The prevalence of hepatitis B virus infection appears to be decreasing in South African Chinese, probably because improved hygienic and socioeconomic circumstances, in comparison with those in Guangdong, have resulted in less horizontal transmission of the virus. A diminishing pool of carriers is maintained by perinatal maternal-infant infection.

Perinatal transmission of hepatitis B virus: role of maternal HBeAg and anti-HBc IgM.

The development of hepatitis B surface antigen (HBsAg) carrier states in newborns of HBsAg-positive mothers was correlated to the presence of anti-HBc IgM and HBeAg in the mothers. There was a positive correlation between infection of the newborn and the presence of HBeAg, as shown previously, but no correlation with anti-HBc IgM.

Hepatitis B vaccination in high-risk infants: 10-year follow-up.

The long-term efficacy of hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders, immunized at birth in Taiwan during 1981-1984 and followed to age 10 years, via life table survival and Cox multivariate analyses. At 10 years, cumulative persistence of antibody to hepatitis B surface antigen (anti-HBs) was 85%, and cumulative incidence of hepatitis B virus (HBV) infection was 15%. Three children became carriers. Twelve-month anti-HBs titer was the strongest predictor of efficacy. The higher the initial titer, the lower the risk of anti-HBs loss (relative risk [RR], 0.26 for titer of 100-999 mIU/mL; RR, 0.08 for titer >1000 mIU/mL; P<.001) and HBV infection (RR, 0.55 and 0.27; P<.05). Maternal hepatitis B e antigen positivity but not hepatitis B immunoglobulin dose or gender predicted greater antibody persistence to age 10 years. Because the level of antibody persistence remained high and few became carriers, booster revaccination within 10 years seems unnecessary.

Studies of rheumatoid arthritis among a tribe of Northwest Indians.

Thirty-six women from a Northwest Indian population known to have an increased prevalence of rheumatoid arthritis were studied. The course of the clinical disease was that of erosive rheumatoid arthritis with characteristic involvement of metacarpophalangeal and wrist joints. Rheumatoid factor and antinuclear antibody tests were frequently positive, and reactions to gold therapy were more frequent than in other rheumatoid populations. Viral antibodies were similar in the rheumatoid and the control groups. HL-A W24 and HL-A BW40 were increased in both the diseased and the control Indian populations.

The e antigen and vertical transmission of hepatitis B surface antigen.

The relationship of e antigen (eAg) and its antibody (anti-e) to vertical transmission of hepatitis B surface antigen (HBsAg) from chronic asymptomatic HBsAg carrier women to their children was investigated in Taiwan. Sera from 20 of the 62 women studied were positive for eAg (32%); serum from only one woman was positive for anti-e (2%). A total of 85% of the babies born to eAg positive mothers became HBsAg carriers, while only 31% of the babies became carriers when the mother was eAg negative. Maternal e antigenemia correlated with a high HBsAg titer, and both parameters were equally good predictors of vertical transmission.