Random coil conformation of a Gly/Ala-rich insert in IkappaB alpha excludes structural stabilization as the mechanism for protection against proteasomal degradation

BACKGROUND: In recent years, mortality from lung cancer has increased rapidly in Korea, a South East Asian country with a high prevalence of smoking. The objectives of this study are to examine how age, period, and birth cohort effects contributed to trends in lung cancer mortality in Korea 1980-1994, and to predict lung cancer mortality rates for 1995-2004. METHODS: Age- and sex-specific lung cancer mortality rates were obtained from annual reports of the National Office of Statistics in Korea. Poisson regression models were used to estimate age, period and cohort effects. RESULTS: Among men, age-adjusted annual mortality rates from lung cancer (per 100000) increased from 3.7 in 1980 to 17.8 in 1994; corresponding rates for women were 1.4 and 7.0. As age increased, mortality rates from lung cancer increased more rapidly in men than in women. Within the same age group, the mortality of younger cohorts was higher than older cohorts. The average annual number of lung cancer deaths projected for the years 2000-2004 among men and women will be 15441 and 3572 respectively, while the average annual age-adjusted mortality rates from lung cancer (per 100000) will be 65.4 for men and 15.1 for women. These rates correspond to 17.7- and 10.7-fold increases over the 1980 mortality rates in men and women, respectively. CONCLUSION: These results, in conjunction with trends in tobacco consumption, indicate that mortality from lung cancer in both men and women will increase substantially through the early part of the 21st century in Korea.     

Colorectal cancer incidence and survival among Alaska Natives, 1969-1993

BACKGROUND: Although colorectal cancer rates are low among most groups of Native Americans in North America, rates for Alaska Natives have been substantially elevated compared with US rates for all races combined. METHODS: To better describe the epidemiology of colorectal cancer incidence and survival among Alaska Natives, stratified by gender and tribal/ethnic affiliation, we examined data collected by the Alaska Native Cancer Registry 1969-1993. We calculated age-adjusted and age-specific incidence as well as actuarial survival rates, and examined histological type, site, stage at diagnosis, and treatment. We compared these data to colorectal cancer data from whites living in western Washington. RESULTS: In all, 587 colorectal cancer cases were identified among Alaska Natives over the 25-year period, for an age-adjusted annual incidence rate of 71.4/100000 in women, and 69.3/100000 in men. Compared to Alaska Indians, colon cancer rates were significantly higher in Aleuts (relative risk [RR] = 1.6, 95% CI: 1.2-2.2) and in Eskimos (RR = 1.5, 95% CI: 1.2-1.8), while rectal cancer rates did not differ by race/ethnicity. Alaska Natives experienced a 50% higher incidence rate of colorectal cancer overall compared to western Washington whites (RR = 1.5, 95% CI: 1.3-1.6), although rectal cancer rates were similar in the two populations. The highest RR were seen among Alaska Native women; Aleuts and Eskimos had colon cancer rates more than twice that of western Washington white women. No unusual qualitative features were found in the cancers occurring in Alaska Natives. Actuarial colorectal cancer survival rates for Alaska Natives overall were 74% at one year and 42% at 5 years; these rates were very similar to those observed for the western Washington population. Both one and 5-year survival rates showed a significant trend towards improvement over time. CONCLUSIONS: Alaska Natives had substantially higher colorectal cancer incidence rates compared to western Washington whites. Rates were particularly high for Aleut and Eskimo women. These data suggest a need for intensified secondary prevention strategies for this high-risk population, while further research is needed to identify modifiable risk factors.     

Contrast enhancement using the triggered imaging

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.     

Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation

BACKGROUND: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.     

Trends in incidence rates of adenocarcinoma of the oesophagus and gastric cardia in New Zealand, 1978-1992

BACKGROUND: Increasing incidence rates for adenocarcinomas of the oesophagus and gastric cardia have been reported from the United States, Denmark, United Kingdom, Switzerland, and Sweden. This paper reports on the incidence of adenocarcinomas of the oesophagus and gastric cardia in New Zealand in the Maori (Polynesian), and non-Maori (predominantly European) populations. METHODS: Incidence data from the National Cancer Registry for 1978 through 1992 were used to compute age-adjusted rates by sex, ethnic group, anatomic subsite, morphology, 14 area health districts, and for three periods: 1978-1982, 1983-1987 and 1988-1992. Statistical tests for significance of trends and differences in frequencies were employed. RESULTS: Incidence rates for adenocarcinoma of the oesophagus are increasing in non-Maori men and women, but at a lesser rate than that reported for the US. The rate of 2.3 per 100000 population (1988-1992) for non-Maori men is similar to the rate for US white men of 2.5 (1988-1990). Rates for adenocarcinoma of the gastric cardia in non-Maori men declined from 2.5 in 1983-1987 to 1.9 in 1988-1992, and were stable at 0.4 in non-Maori women. However, rates for cases with unspecified anatomic subsite fluctuated over the 15-year period and probably caused a deflation in rates in the most recent 5-year period. CONCLUSIONS: The incidence patterns of adenocarcinomas of the oesophagus and gastric cardia in New Zealand should be monitored over the next decade for confirmation of the trends observed here. There is need to review the quality of the data in the New Zealand registry.     

Prostate cancer in American Indians, New Mexico, 1969 to 1994

PURPOSE: Prostate cancer is the most frequently diagnosed cancer as well as the leading cause of cancer death among American Indian men. MATERIALS AND METHODS: To describe further the occurrence of prostate cancer among American Indian men, we examined population based incidence, treatment, survival and mortality data for American Indians in New Mexico during the 25-year period 1969 to 1994. RESULTS: Although American Indian men have a lower risk of prostate cancer than nonHispanic white men, the incidence and mortality rates are rising for American Indians, and mortality rates are now equal to those for nonHispanic white men. During the 25-year period age adjusted incidence rates for American Indians increased from 42.2/100,000 (95% confidence interval 27.1 to 57.3) to 64.6/100,000 (95% confidence interval 46.2 to 83.0). The burden of prostate cancer among American Indian men compared with nonHispanic white men was reflected in disproportionately high mortality rates in relation to incidence rates. The mortality rates were high because American Indian cases were more advanced at diagnosis, 23.3% of prostate cancers were diagnosed after distant spread had occurred compared with 11.6% for nonHispanic white men and the 5-year relative survival rate was poorer (57.1% compared with 77.6% for nonHispanic white men). CONCLUSIONS: Effective and culturally sensitive cancer control efforts for prostate cancer in American Indian communities are urgently needed.     

Screening patients with celiac disease for primary biliary cirrhosis and vice versa

BACKGROUND: An association between celiac disease and primary biliary cirrhosis has been reported in a few cases, mainly as individual case reports. OBJECTIVES: To screen adult patients with celiac disease for primary biliary cirrhosis and patients with primary biliary cirrhosis for intestinal celiac involvement. METHODS: The celiac group consisted of 336 adults (218 women and 118 men; mean age, 36 yr; range 18-74 yr) with celiac disease diagnosed by serological and histological tests, 38 with newly diagnosed celiac disease and 298 with previously diagnosed celiac disease who were consuming a gluten-free diet. The mean follow-up period was 6 yr (range, 1-16 yr). Liver function parameters and autoantibody levels were determined, and, when indicated, histological tests were performed. The biliary cirrhosis group consisted of 65 subjects (58 women and seven men) (mean age, 59 yr; range, 35-67 yr) with primary biliary cirrhosis diagnosed 1-17 years previously (mean, 7 yr) on the basis of the usual biochemical, serological, and histological criteria. Antigliadin and antiendomysium antibody levels were determined, and two biopsy specimens from the distal duodenum obtained during endoscopy were evaluated. RESULTS: In patients with celiac disease, impairment of liver function was frequently found at diagnosis (16 of 38, or 44%), but primary biliary cirrhosis was diagnosed in only one case. In patients with primary biliary cirrhosis, no cases of celiac disease, as currently defined, were found. CONCLUSIONS: Our findings indicate that celiac disease and primary biliary cirrhosis are rarely associated and support the hypothesis that the intestinal lesions per se are not responsible for the liver disease.     

Attributable risk for symptomatic liver cirrhosis in Italy. Collaborative Groups for the Study of Liver Diseases in Italy

BACKGROUNDS/AIMS: Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports. METHODS: The proportion of newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989-1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection. The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk. RESULTS: Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5-7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI: 81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women. CONCLUSIONS: Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the well-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis should become a rare disease.     

Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis

PURPOSE: To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. METHODS: 967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study. Monitoring for hepatocellular carcinoma was scheduled at 3- to 6-month intervals. The mean (+/-SD) length of follow-up was 60.3+/-51.7 months (range 6 258). RESULTS: During the observation period, hepatocellular carcinoma developed in 64 patients. The calculated annual incidence was 2.1%. The probability of being free of liver cancer was 92% at 5 years, 80% at 10 years, and 69% at 15 years. Age was the only independent risk factor for the development of malignancy in the multivariate analysis. There were no differences according to male sex, alcohol abuse, and chronic hepatitis B and C virus infection. CONCLUSIONS: The annual incidence of hepatocellular carcinoma was 2.1%. These results, although confirming that age is a risk factor for hepatocellular carcinoma in cirrhosis, indicate that alcohol abuse, male sex, and concurrent hepatitis B and C virus infection do not involve a higher risk of developing liver cancer.     

Acute myocardial infarction case fatality, incidence and mortality rates in a population registry in Gerona, Spain, 1990-1992. REGICOR Investigators

BACKGROUND: Community-based registries provide the best approach to assessing the impact of myocardial infarction (MI) in a population. The objective of the present study was to determine MI mortality, incidence, attack rate and 28-day case fatality in the province of Gerona, Spain from 1990 to 1992. METHODS: Standardized methods were used to find, register and classify MI cases in that population (509628 inhabitants) as definite, possible and insufficient-data MI. RESULTS: Of the 1456 cases fulfilling eligibility criteria, 850 (58.4%) were classified as definite MI, 162 (11.1%) as fatal possible MI, 232 (15.9%) as no MI and 160 (11.0%) as fatal insufficient data. The 1990-1992 age-standardized incidence rates (first MI cases only) for definite and fatal possible MI were 140.8 per 100000 men and 20.4 per 100000 women, all aged 35-64 years; attack rates (first and recurrent MI cases) were 182.9 and 24.5, and mortality rates 46.4 and 5.8, respectively. Case fatality at 28 days was 27.4% and 19.9% in men and women, respectively, but women died later over that period. With respect to men, the age-adjusted risk among women of dying within 28 days post-MI was 1.26 (95% confidence interval [CI]: 0.94-1.69). CONCLUSIONS: Myocardial infarction, incidence, mortality rates and case fatality in Gerona are among the lowest in the world. Age-adjusted case fatality within 28 days is only marginally higher in women than in men, but fatal cases occur later within this period in women.     

Alcohol-related harm and alcohol consumption in Moscow before, during and after a major anti-alcohol campaign

AIMS: To examine the rates of alcohol-related harm in relation to levels of alcohol consumption before, during and after a major anti-alcohol campaign in Moscow. DESIGN: Changes in State alcohol sale and alcohol consumption and certain forms of alcohol-related harm were observed as a function of time. FINDINGS: Following the 1985 anti-alcohol campaign, State alcohol sales decreased by 38.0% in 1.5 years in Moscow, and total consumption decreased by 28.6%. At the same time, admissions for alcohol-related mental and behavioural disorders, deaths from liver cirrhosis, alcohol poisoning and other blood alcohol positive violent deaths decreased by 63.3%, 33.0%, 50.8% and 50.9%, respectively. There was a linear correlation between medical variables and alcohol consumption during its decrease in 1985-86. An increase in blood alcohol positive violent deaths began in 1987, before the increases in other variables. Growth of total alcohol consumption began in 1987, and continued during all subsequent years, although it was especially high in 1992-93 at the time of the introduction of market reforms in Russia. Alcohol-related mental and behavioural disorders and liver cirrhosis mortality increased after a time-lag following the rise in alcohol consumption. CONCLUSIONS: The findings provide stark evidence of the potential impact of policy measures applied to general alcohol consumption on alcohol-related harm.     

Prospective use of glycoprotein IIb/IIIa receptor blockers in the emergency department setting

OBJECTIVE: We examined whether alcohol consumption and problem drinking decreased with age or if the reported declines were actually cohort and/or period effects. METHOD: We utilized data from the Normative Aging Study, assessing 1,267 men three times over an 18-year period (1973, 1982, 1991). Men were divided into five 9-year birth cohorts; age ranged from 46 to 72. RESULTS: Sequential analyses using repeated measures ANOVAs showed significant age, cohort and period effects. Although there was a tendency for alcohol consumption to decline with age, this was not true for all cohorts. Men born between 1910 and 1918 increased from an average of 350 to 440 drinks per year from their fifties to their sixties. The younger cohorts tended to report both more consumption and more problems. However, period had the most consistent effect in this study. There was an increase in problems and in consumption during the 1970s but a decrease in the 1980s, with the exception of the youngest cohort (1937-1945) who reported more problems in the 1991 assessment despite lower consumption. CONCLUSIONS: Age-related change in both consumption and problems varied depending upon which cohort or time period was assessed. Thus, drinking patterns are a complex amalgam of individual aging and societal change.     

Cognitive bibliotherapy for mild and moderate adolescent depressive symptomatology

OBJECTIVE: To compare patterns of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) mortality in 11 selected industrialized countries with highly developed death registration systems and a broad range of cumulative AIDS incidence rates. METHODS: Data on HIV/AIDS mortality were obtained from the World Health Organization (WHO) and Statistics Canada for the years 1987-1991. We obtained data for Australia, Canada, Denmark, France, the former Federal Republic of Germany, Italy, the Netherlands, New Zealand, Spain, Switzerland, and the US, stratified by sex and 5-year age groups. Population figures were obtained from national censal, post-censal or interpolated annual estimates compiled by WHO and from Statistics Canada. RESULTS: A total of 141534 deaths were attributed to HIV/AIDS (126224 in men and 15310 in women) in the 11 countries from 1987 to 1991. The majority of deaths (73.7%) occurred in the US. Other countries contributing substantially to the number of deaths were France (7.1%), Italy (4.9%), Spain (4.9%), former West Germany (3.5%), and Canada (3.0%). Age-specific death rates for men aged 25-44 years in 1991 were highest in the USA at 47.1 per 100000 population and highest for women in Switzerland at 7.7 per 100000 population. Potential years of life lost (PYLL) before age 75 years were highest for males in the US (2388 per 100000 population) and for females in Switzerland (373 per 100000 population). The lowest rates were in New Zealand (339 per 100000 population in men and 6.5 per 100000 population in women). CONCLUSIONS: This historical demographic analysis indicates that mortality resulting from HIV infection and AIDS among men and women varies considerable by country. Rates of death were highest in the US and lowest in Australia, the Netherlands, and New Zealand.     

Early results of a prospective study of hormone therapy for patients with locally advanced prostate carcinoma

BACKGROUND: Locally advanced prostate carcinoma is usually not curable with surgery or radiation therapy. Primary hormone therapy is an alternative therapeutic option, but contemporary prospective studies of the outcomes of such therapy are not available. METHODS: The authors conducted a prospective, hospital-based study of gonadal androgen ablation with deferred antiandrogen therapy in 103 men with prostate carcinoma clinically classified as T3-4NXM0. The median potential follow-up was 51 months (range, 36-74 months), and the median period of observation was 43 months (range, 6-74 months). RESULTS: Each patient experienced regression of the primary tumor, and none experienced significant morbidity from the primary tumor during the study period. The projected 5-year cause specific, metastasis free, PSA disease free (no PSA elevation > 1.0 ng/mL after the beginning of antiandrogen therapy), and all-cause survival rates were 84%, 84%, 68%, and 58%, respectively. CONCLUSIONS: Primary hormone therapy is a reasonable treatment option for locally advanced prostate carcinoma in elderly men or in men with significant comorbid disease who request therapeutic intervention.     

Two cases of delayed posttraumatic vasospasm followed by brain SPECT

OBJECTIVES: To describe the incidence of Guillain-Barré syndrome in Sweden during the period 1978-93 and its temporal and geographical variations. METHODS: Stratified and Poisson regression analyses and tests for detection of small epidemics were applied to population based hospital discharge data from 2257 incident cases of Guillain-Barré syndrome in Sweden during the study period. RESULTS: The incidence of Guillain-Barré syndrome was (1) 1.77 per 100000 person-years when age adjusted to the European population; (2) higher in males; and (3) stable across time, although occasional increases of annual incidence rates were found-namely, in 1978 (relative risk (RR) 1.30 (95% CI 1.10-1.54)), and in 1983 (RR 1.24 (95% CI 1.06-1.40)). The incidence increased with age and was bimodal, with peaks at 20-24 and 70-74 years. There was a moderate but significant seasonality with a peak in August, particularly among the young age groups. The age adjusted incidence by county varied from 1.11 to 2.57 per 100000 person-years. Neither temporal nor spatial clustering was significant, except during the period July-September in 1983 at ages below 40 years. CONCLUSIONS: The incidence of Guillain-Barré syndrome in Sweden during the period 1978-93 had a magnitude similar to those described in other surveys, a bimodal distribution by age, and modest geographical and temporal variations with significantly high rates in 1978 and 1983 and in autumn. Minor outbreaks might have passed unnoticed up to the present. Whereas reported drug induced cases of Guillain-Barré syndrome may in part explain the high incidence in 1983, the cause of the aberrant incidence in 1978 remains unknown. Epidemiological surveillance of Guillain-Barré syndrome in Sweden might have been useful.     

Treatment of aggression and irritability after head injury

Epidemiological characteristics of colorectal cancer may differ by particular anatomical subsite, suggesting that the subsite-specific colorectal cancers may represent different disease entities. This study explored the time trends over a 23-year period in colorectal cancer incidence at various subsites by sex and age group. Data on the incidence of colorectal cancer were obtained from a population-based cancer registry in Shanghai, People's Republic of China. Between 1972 and 1994, 30,693 patients with colorectal cancer were registered at the Shanghai Cancer Registry. The overall age-adjusted colorectal cancer incidence rates increased > 50%, or 2% per year from 1972-1977 to 1990-1994, from 14 to 22 per 100,000 among men and from 12 to 19 per 100,000 among women. The increases in rates were considerably more rapid for colon cancer, with rates approximately doubling, than they were for rectal cancer. Proximal colon cancer was more common than distal colon cancer over the whole study period, whereas rates for both cancers rose with similar annual percentage changes (> 5% per year) and across virtually all age groups. The estimated annual increases rose from 2% at ages 35-44 years to 7% at ages 75-84 years for proximal colon cancer, but they were more uniform for distal colon cancer (5-6% per year). Age-adjusted and age-specific rectal cancer rates changed little. The male:female age-adjusted rate ratio for colorectal cancer was 1.19 in 1990-1994. The ratios increased over time and varied by subsites, with ratios increasing from the proximal colon to the distal colon and to the rectum. Furthermore, men had higher rates than women for distal colon and rectal cancers at ages 55 and older, whereas women had higher rates than men at younger ages for these two cancers. Male:female rate ratios for proximal colon cancer did not vary substantially with age. The findings from this study indicate that subsite-specific incidence rates of colorectal cancer differ by sex and age and in their time trends. Cancers arising in the proximal colon, distal colon, and rectum may have somewhat different disease etiologies.     

Double wave cohort increase for oesophageal and laryngeal cancer in France in relation to reduced alcohol consumption during the second world war

Mortality from oesophageal cancer is increasing in France. A cohort analysis indicates that there were two successive waves of increase separated by a non-increase interval for the cohorts born between 1902 and 1916. A similar effect was observed for laryngeal cancer and liver cirrhosis but not for lung and pancreas cancer. This might be related to the reduction of alcohol consumption during the second world war.     

Structure of CheA, a signal-transducing histidine kinase

BACKGROUND/AIMS: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years). RESULTS: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well. CONCLUSIONS: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.     

The "epidemic" of breast cancer in the U.S.--determining the factors

Breast cancer incidence rates in the United States rose by 24% between 1973 and 1991. Mortality during this period, however, remained stable. Both the 5-year relative survival rate and the rates of in situ and stage I breast cancers have been increasing, while the incidence of later-stage cancers has been decreasing. Increased mammography screening may explain the documented jump in breast cancer incidence rates during the mid-1980s. Differences in the distribution of breast cancer risk factors may account, in part, for the temporal trends in breast cancer incidence. In particular, breast cancer risk factors may vary by birth cohort, including age at menarche, age at first birth, physical activity, obesity, diet, alcohol intake, estrogen therapy, and exposure to environmental organochlorines. After decades of epidemiologic research, a preventive approach to breast cancer that focuses on the physiologic effects of the sex steroid hormones, and their potential interactions with family history, is being carefully formulated.