Characterization of mutant Bordetella pertussis adenylate cyclase toxins with reduced affinity for calmodulin. Implications for the mechanism of toxin entry into target cells

BACKGROUND: Data and statistics are presented on cancer death certification for 1993 in Italy, updating previous publications covering the period 1955-1992. METHODS: Data for 1993 subdivided into 30 cancer sites are presented in 8 tables, including age- and sex-specific absolute and percentage frequencies of cancer deaths, and crude, age-specific and age-standardized rates, at all ages and truncated for the 35-64 year age group. RESULTS: Age-adjusted death certification rates (on the world standard population) for all neoplasms declined from 189.8 in 1992 (and a peak of 199.2 in 1986) to 187.8/100,000 males in 1993, and remained stable around 100,000 females. The favorable trends were even larger in middle and younger age males, but not in children below age 15, whose overall age-standardized cancer mortality rates increased for the fourth subsequent year. Lung cancer was the leading site of cancer mortality, with over 30,900 deaths. For the fifth subsequent year, its rates in males declined, to reach 56.0/100,000. The decline in lung cancer rates is now established in Italian males and is substantial in middle age, whereas the rise in female lung cancer rates seems to have leveled off over the last few years. Rates for other major cancer sites (intestines, stomach, female breast, prostate, pancreas, leukemias and lymphomas) were stable, but some decrease was apparent also in 1993 for Hodgkin's disease. CONCLUSIONS: Italian cancer mortality rates in 1993 were moderately favorable in males, due to the leveling of the tobacco-related epidemic, whereas no appreciable change was registered in females. The persisting unfavorable trends in childhood cancer mortality should be investigated.     

Descriptive epidemiology of vulvar and vaginal cancers in Vaud, Switzerland, 1974-1994

BACKGROUND: To analyse trends in incidence, survival and risk of second neoplasms following vaginal and vulvar cancers using data collected by the Swiss Cancer Registry of Vaud over the 21-year period 1974-1994. MATERIALS AND METHODS: Subjects were 257 vulvo-vaginal cancers. Of these, 69 were vaginal, 153 vulvar cancers, and 35 non-specified lower genital tract neoplasms; 94 in situ neoplasms were also registered (85 for the vulva). RESULTS: Invasive vaginal cancer incidence decreased from 0.8 in 1974-1984 to 0.4/100,000 women in 1985-1994, while invasive vulvar cancer incidence remained approximately stable around 1.2/100,000 (world standard); incidence of in situ vulvar cancer increased from 0.8 to 1.3/100,000, the rise being larger in younger women. Significant excesses for second primary neoplasms were observed for pro-pharyngeal and lung cancer, and for non-melanomatous skin neoplasms, as well as for invasive vulvar cancers following in situ cancers. CONCLUSIONS: This population-based dataset confirms that the incidence of in situ vulvar (but not invasive vulvar or vaginal cancer) has been increasing over the last 20 years. The excess second primary neoplasms supports the hypotheses that human papillomavirus and cigarette smoking are related to vulvo-vaginal neoplasms.     

Trends in non-epithelial cancer incidence in Denmark, Finland, and Sweden, 1961-1990

Trends in the incidence of non-epithelial cancers are particularly likely to reflect environmental carcinogens, since these malignancies are not commonly the targets of screening efforts, and have generally not been closely associated with life style factors such as cigarette smoking and diet. We used data from nation-wide cancer registries in Denmark, Finland, and Sweden to examine trends in non-epithelial cancers over the period 1961-1990. Linear regression analysis of age-standardized rates, and age-period-cohort models were fit to assess the temporal patterns within each country. Within each of the 3 countries, there was a similarly increasing incidence of both hematological malignancies and nervous system/bone/soft-tissue neoplasms. The increases were smallest in children and adolescents (ages 0-14), moderate among young and middle aged adults (ages 15-64), and most pronounced among the elderly (ages 65+). Age-period-cohort modeling suggested that the dominant factor in the increases were birth cohort effects. It is not clear what factors underlie this increase in incidence; it seems most likely that increases both in diagnostic efficiency and in exposure to environmental carcinogens play a role.     

Childhood poisoning: a population study in Trieste, Italy, 1975-1994

We describe the epidemiology of 1918 cases of childhood poisoning referred to the emergency room in Trieste, Italy, from 1975 to 1994. The incidence rate of emergency room referral and subsequent hospitalization was calculated on the basis of the distribution of children resident in Trieste by calendar year. The occurrence of childhood poisoning was described according to time trends, age and gender of the child, route of exposure, symptoms at presentation to the emergency room, role of the child or others, intention, and substance involved in the poisoning. The association between presence of symptoms and characteristics of referral, host factors and substances involved was evaluated by estimating the odds ratio in multivariate models. Possible determinants of the clinical decision to treat certain cases were evaluated using logistic regression. Despite an increasing incidence of referral (from 155 per 100,000 persons per year in 1975-79 to 352 per 100,000 in 1990-94), hospital admission rates showed a two-fold decrease. Younger children (age 0-4 years) were more likely to be asymptomatic and required treatment and hospitalization less often than older children (age > or = 10 years). Trends show a decrease in pharmaceutical poisonings due probably to the introduction of child-resistant containers and an increase in domestic poisons. We also observed a steady increase in carbon monoxide inhalation and alcohol poisonings, mostly among teenagers.     

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.     

Poisoning mortality, 1985-1995

Poisoning was reported as the underlying cause of death for 18,549 people in the United States in 1995 and was ranked as the third leading cause of injury mortality, following deaths from motor vehicle traffic injuries and firearm injuries. Poisoning was the leading cause of injury death for people ages 35 to 44 years. Poisoning death rates were higher in 1995 than in any previous year since at least 1979. From 1990 to 1995, the age-adjusted rate of death from poisoning increased 25%; all of the increase was associated with drugs. About three-fourths of poisoning deaths (77%) in 1995 were caused by drugs. The age-adjusted rate of drug-related poisoning deaths for males (7.2 per 100,000) in 1995 was more than twice that for females (3.0 per 100,000). From 1985 to 1995, poisoning death rates for males ages 35-54 years nearly doubled to 20.4 per 100,000, and the drug-related poisoning death rate for males ages 35-54 years nearly tripled, reaching 16.1 per 100,000. From 1990 to 1995, death rates associated with opiates and cocaine more than doubled among males ages 35-54 years. The numbers of opiate and cocaine poisoning deaths for 1995 more than doubled when all multiple cause of death codes were examined instead of only the underlying cause of death codes.     

Descriptive epidemiology of body mass index in Japanese adults in a representative sample from the National Nutrition Survey 1990-1994

OBJECTIVE: To determine the prevalence of obesity and reference percentile curves of body mass index (BMI; kg/m2) in Japanese adults. DESIGN: Cross-sectional nationwide surveys (The National Nutrition Survey, Japan) carried out in 1990-1994. A sample of 23,556 males and 28,751 females aged 15-84 y was used for this analysis. RESULTS: The prevalence of grades 1 (BMI: 25.0-29.9), 2 (30.0-39.9) and 3 (> or = 40.0) overweight, was estimated to be 24.3%, 1.84% and 0.019% in males, respectively, and 20.2%, 2.87% and 0.032% in females, respectively, subjects aged 35-64 y after standardization to the age-distribution of the standard world population (WHO, 1993). The age-standardized prevalence of obesity (for BMI > or = 26.4, a criterion of the Japan Society for the Study of Obesity; and > or = 30.0 was 13.6% and 1.86% in males, respectively, and 13.5% and 2.90% in females, respectively, subjects aged 35-64 y. CONCLUSIONS: The standardized prevalence of obesity (BMI > or = 30.0) in Japanese adults was quite low compared with the data in western populations.     

Age-specific incidence of cancer in Kingston and St. Andrew, Jamaica, 1988-1992

During the period 1988-1992, a total of 4,030 malignant neoplasms were recorded in Kingston and St. Andrew, Jamaica. These comprised 1,829 in males and 2,201 in females. Histological confirmation was obtained in 83.4%. The crude incidence rate for males was 128.5, and 136.2 for females. The age-standardized rates (ASR) were 179.9 for males and 166.1 for females. Age-specific rates by site, sex and age are tabulated. Attention is drawn to increased incidence for cancers of prostate, larynx, bronchus and non-Hodgkin's lymphoma in males. There was also an increase in female breast cancer (crude rate 36.0; ASR 47.1). Invasive cervix cancer has shown no significant change in incidence. Neoplasms of the body of the uterus have increased (crude rate 7.6; ASR 9.5). The rise in cancer of breast and body of uterus suggests that the influence of exogenous oestrogens should be considered.     

Use of lipid-lowering drugs from 1990 to 1994: an international comparison among Australia, Finland, Italy (Emilia Romagna Region), Norway and Sweden

OBJECTIVE: To compare the overall utilisation pattern of lipid-lowering drugs between 1990 and 1994 in Australia, Finland, Italy, Norway and Sweden as well as the pattern of use with respect to age and gender in Italy and Sweden. METHODS: Data were retrieved from regulatory authorities in each country for the 5-year period and analysed according to the ATC/DDD methodology (Anatomical Therapeutic Chemical classification/Defined Daily Doses). Utilisation was calculated as the DDDs for 1000 inhabitants per day for all drugs of the ATC category B04 (serum lipid-reducing agents). Data from Sweden and Italy were also compared with respect to gender and age. RESULTS: In 1994, Australia demonstrated the highest degree of utilisation (11.9 DDD) and the Nordic Countries the lowest (Sweden 5.6; Norway 4.9; Finland 4.0). In all countries except Italy, a steady increase was observed; in Italy, utilisation of these drugs reached a maximum in 1992 (11.5 DDD), but then underwent a reduction which was caused by restrictions in the reimbursement status in 1993 (10.4) and 1994 (6.7). Administration of statins increased in all countries, becoming the most used group of the B04 class. In 1988, the number of different drugs listed by each national health service ranged from 4 (Norway) to 16 (Italy); in 1994 it ranged from 6 (Norway) to 9 (Sweden). Analysis with respect to gender showed the opposite pattern in Sweden (males 4.6 and females 3.3 in 1992; 6.2 and 4.5, respectively, in 1994) than in Italy (males 10.8 and females 17.8 in 1992; 6.4 and 9.2, respectively, in 1994). Exposure was highest in people aged 60-69 years in both countries, followed by age group 50-59 in Sweden and 70-79 in Italy. CONCLUSIONS: Large variations in the utilisation of lipid-lowering drugs exist between countries, with Australia and Italy much higher than others. Of the drugs in the ATC category B04, the use of statins predominates in all countries, but to varying degrees. The large difference in the degree of drug utilisation with respect to age and gender between Italy and Sweden suggests major deviations from evidence-based medicine.     

Changes in alpha (1-2)-fucosyltransferase activity in the murine endometrial epithelium during the estrous cycle, early pregnancy, and after ovariectomy and hormone replacement

The ratios of age-standardized mortality rates of Aboriginals to non-Aboriginals in Western Australia during the period 1983-1989 were 2.6 for males and 3.0 for females. Mortality rates experienced by Aboriginals were much higher in all age categories except 75+ years and for most major diseases except neoplasms. The peaks of all-cause age-specific mortality rate ratios (RR) for Aboriginal males and females were 10.2 (at 40-44 years) and 10.0 (at 35-39 years), respectively. These excess mortalities were mainly due to circulatory diseases, injury and poisoning, respiratory diseases and, in females, to digestive diseases and genitourinary diseases. The highest age-standardized, cause-specific RR for Aboriginal males were for mental disorders (10.3), injury and poisoning (8.9) and genitourinary diseases (8.6); for females the highest RR were for genitourinary diseases (16.9), endocrine, nutritional and metabolic (mainly diabetes mellitus) (12.3), and for infectious and parasitic diseases (7.5).     

Childhood cancer incidence and trends in Minnesota, 1988-1994

Childhood cancer incidence patterns for Minnesota, obtained from the Minnesota Cancer Surveillance System, were compared with national rates as well as with historic data from eight Minnesota counties. In total, 1,140 neoplasms were diagnosed in children (ages 0 to 14) between 1988 and 1994. Leukemias were the most common diagnosis for boys (30.3%) and girls (29.6%), followed by central nervous system tumors. The average annual age-adjusted incidence rates for all cancer sites were 167.2 and 136.2 per million for boys and girls, respectively. These rates were somewhat higher than national rates. In particular, the incidence rate for astrocytoma in boys was significantly elevated. Childhood cancer incidence, particularly brain tumors, has increased in the eight-county region from 1969 to 1994. This analysis demonstrated the Minnesota's childhood cancer incidence patterns are similar to national patterns.     

Mortality patterns and trends for lung cancer and other tobacco-related cancers in the Americas, 1955-1989

Mortality from cancers of the oral cavity and pharynx, oesphagus, larynx and lung between 1955 and 1989 has been analysed for USA, Canada and 14 countries in Latin America. Among males, Uruguay, Cuba, Argentina and Puerto Rico have the highest rates for all sites, and Peru, Ecuador, Dominican Republic, Mexico and Colombia have the lowest rates. Among females, Cuba, Colombia and Puerto Rico rank high for all sites, and Mexico, Paraguay, Ecuador and Peru rank low. For both sexes, lung cancer mortality rates from the US and Canada are high, whereas rates from other sites are intermediate. An increasing trend in lung cancer mortality over time is shown in all countries except Cuba (no changes), Argentina, Paraguay and Peru (decreasing trend). In Latin America, the tobacco-related lung cancer epidemic is in its early phase among males, and very early phase among females.     

Differential features of motor neuron disease mortality in Spain

BACKGROUND: The objective of this study was to describe the temporal and spatial patterns of motor neuron disease (MND) in Spain. METHODS: We studied data where MND was stated as the principal cause of death in official statistics from Spain. Time trends were analysed for age-, sex-specific and age-adjusted rates for the period 1951-1990. Age-adjusted mortality and relative risk, obtained by Poisson regression adjusting for age, were calculated for each province from deaths during the period 1975-1988. Maps were constructed using log transformed rates. Statistical significance of spatial aggregation was assessed using the Ohno et al. test. RESULTS: The 1951-1990 mortality rate, age- and sex-adjusted to the European population, for the population aged > or = 40 years was 1.49 per 100,000; 1.90 and 1.21 for males and females respectively. In general, mortality increased with age. Age-adjusted rates rose until 1960, dropped by 70% during the 1960s and declined slightly over the 1951-1990 period as a whole. From 1970 onwards MND mortality rose evenly, particularly in the 60-69 age group. A North-South gradient was suggested for both sexes with statistically significant clustering in the Northern coastal regions and--for males alone--in the Midwest provinces. CONCLUSIONS: Mortality from MND in Spain displayed a magnitude and recently rising temporal trend similar to that described in several other countries. Specific traits were: a decrease during the 1960s, which has been described for Japan only, as well as spatial heterogeneity and a predominant recent increase among the 60-69 age group. The determinants of these unusual MND mortality patterns are unknown.     

Trends in cigarette consumption cannot fully explain trends in British lung cancer rates

STUDY OBJECTIVES: To determine whether British lung cancer (LC) trends are adequately explained by cigarette smoking trends, and whether modelling using aggregated smoking prevalence estimates can validly replace modelling using individual smoking histories. METHODS: Observed LC trends for 1955-1985 for both sexes and three age groups were compared with multistage model predictions using smoking history data from two surveys (HALS, AHIP). The modelling used the individual smoking data directly or aggregated prevalence estimates. It allowed for variation in age of starting and stopping smoking, amount smoked, tar levels, and environmental tobacco smoke (ETS) exposure. RESULTS: Observed male LC rates fell faster than predicted by a model (with the first and penultimate stages assumed affected by smoking) that allowed for variation in amount smoked and in tar level (with some provision for "compensation"), and was based on aggregated smoking data from HALS. The discrepancy equated to an annual change unexplained by smoking of -2.4%, -2.8%, and -1.9% for ages 35-44, 45-54, and 55-64. The annual unexplained changes were less in women, and reversed at age 55-64; -1.7%, -0.8%, and +0.8% for the three ages. They were similar using individual smoking histories (-2.6%, -1.8%, and -1.6%; women, -0.9%, -0.5%, and +0.2%). The discrepancies were unexplained by plausible alternative multistage parameters, full allowance for tar reduction, alternative estimates of amount smoked, or ETS. CONCLUSIONS: British LC trends cannot be fully explained by cigarette consumption trends, implying factors other than cigarette smoking contribute importantly to overall risk. Predictions using aggregated prevalence estimates provide useful information.     

Suicide trends in eight predominantly English-speaking countries 1960-1989

Suicide rates between 1960 and 1989 were explored for eight predominantly English speaking countries with similar national characteristics. New World countries showed significant similarities but differed from Old World countries. The two North American (NA) New World countries showed more similarity to each other than the two Australasian New World countries. The NA countries showed an unique plateau in the 1980s for males aged 15-29 years. Old World males of all ages showed common rises, suggesting a partial sex-specific influence in the young. However, trends among the 15- to 19-year-olds were significantly different to trends among the 20- to 29-year-olds in both sexes suggesting a substantial youth-related contribution to the rises. Rates among 15- to 19-year-old females rose in the early 1960s, ahead of males but in parallel with rises among older females, suggesting part of the rise was sex- as opposed to age-related. Although rates among the 15- to 19-year-old females showed little change since 1970, this may be partly a function of sex-related improvements-observable in older females disguising unfavourable youth-related influences. Possible aetiological factors are suggested but remain speculative. Studies of other nations with common cultural characteristics may clarify trends and aetiological issues. Care should be taken to differentiate sex- from age-related influences.     

The main causes of death in Spain, 1992; comment

BACKGROUND: To study the mortality from the leading causes of death in Spain in 1992 and trends since 1980. POPULATION AND METHOD: The number of deaths was obtained from mortality statistics. We included the 12 causes with the highest mortality rates in 1992 and calculated for each cause of death the age adjusted mortality rates for each year in the study period, the percent change from 1990 to 1992 and from 1980 to 1992, and the adjusted ratio of rates between men and women in 1992. RESULTS: The leading causes of death in 1992 were malignant neoplasms, with 24.3% of deaths and a mortality rate of 205.6 per 100,000 population; diseases of the heart, with 22.6% and a rate of 191.8 per 100,000; and cerebrovascular disease, with 12.7% and a rate of 107.6 per 100,000 population. Between 1980 and 1992 the adjusted mortality rate increased for four causes of death: malignant neoplasms; chronic obstructive pulmonary disease and similar diseases; nephritis, nephrotic syndrome and nephrosis; and suicide. From 1990 to 1992, the adjusted mortality rate declined for all other causes of death. From 1990 to 1992, the adjusted mortality rate declined for all causes of death except for malignant neoplasms and human immunodeficiency virus (HIV) infection, which rose 0.4% and 69%, respectively. The adjusted mortality rate was higher in men than in women for all causes of death except for diabetes mellitus and atherosclerosis. CONCLUSIONS: Except for malignant neoplasms and HIV infection, mortality from all other leading causes of death declined in 1992 with respect to 1990, independently of the trend experienced by each cause of death in the eighties.     

Regional and chronological differences of urogenital cancer deaths in Japan

PURPOSE: We investigated the changing patterns of urogenital cancer deaths during the past 22 years in Japan. METHODS: We analyzed patients that died from cancer of the prostate, bladder and kidney between 1973-1994. Age-adjusted death rates (adjusted to the world population), standardized mortality ratios (SMR) according to each prefectures and age-specific death rates for each types of cancer were calculated and changes in these patterns were analyzed. RESULTS: Age-adjusted death rates for cancer of the prostate increased from 2.29 in 1973 to 4.36 in 1994, a 1.9-fold increase. Death rates for cancer of the bladder were stable in males and declined in females. Death rates for cancer of the kidney (15 years or older) increased from 1.45 in 1973 to 2.72 in 1994, a 1.9-fold increase in males, and tended to increase in females as well. In the SMR analysis by prefecture, distribution in 1973-84 (former period) and that in 1985-94 (later period) were similar, and characteristic features were observed for each type of cancer. Age-specific death rates for cancer of the prostate and bladder rose by an index power of age, but that for cancer of the kidney reached a plateau or decreased after an index power increase to a certain age. The rate of increase in age-specific death rates (later period/former period) rose according to age, especially 70 years or older, in cancer of the prostate and kidney in both males and females. However, age-specific death rates in the later period from cancer of the bladder was higher only in patients 85 years or older, but was lower in other age groups. CONCLUSIONS: Death rates for cancer of the prostate and kidney (15 years or older) tended to increase, while that of the bladder remained stable or decreased. It is expected that detection and treatment of these disease can be improved by utilizing these epidemiologic information.     

Cancer incidence in The Netherlands in 1989 and 1990: first results of the nationwide Netherlands cancer registry. Coordinating Committee for Regional Cancer Registries

The first results are presented of the newly established Netherlands Cancer Registry, which covers the whole Dutch population (approximately 15 million people). The registry receives data on incident cancer cases from nine autonomous regional cancer registries. Notification occurs primarily through the national registry of all pathology and haematology departments, with additional reporting by medical records' departments of all hospitals. Data on cancer patients are abstracted directly from the medical records by trained registration clerks. In the years 1989-1990, the most common cancer sites among males were cancers of the lung, prostate and colon. For females, breast cancer ranked first, followed by cancer of the colon and lung. A comparison with age-adjusted (world standard population) incidence rates reported by other western cancer registries showed a relatively high incidence of lung cancer among males (72.9 per 100,000) and breast cancer among females (76.2 per 100,000). Through its near completeness and the high quality of the registered data, the Netherlands Cancer Registry offers excellent opportunities for epidemiological and clinical research.