Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.     

Body mass index, exercise, and other lifestyle factors in relation to age at natural menopause: analyses from the breakthrough generations study

The authors examined the effect of women's lifestyles on the timing of natural menopause using data from a cross-sectional questionnaire used in the United Kingdom-based Breakthrough Generations Study in 2003-2011. The analyses included 50,678 women (21,511 who had experienced a natural menopause) who were 40-98 years of age at study entry and did not have a history of breast cancer. Cox competing risks proportional hazards models were fitted to examine the relation of age at natural menopause to lifestyle and anthropometric factors. Results were adjusted for age at reporting, smoking status at menopause, parity, and body mass index at age 40 years, as appropriate. All P values were 2-sided. High adult weight (P(trend) < 0.001), high body mass index (P(trend) < 0.001), weight gain between the ages of 20 and 40 years (P(trend) = 0.01), not smoking (P < 0.001), increased alcohol consumption (P(trend) < 0.001), regular strenuous exercise (P < 0.01), and not being a vegetarian (P < 0.001) were associated with older age at menopause. Neither height nor history of an eating disorder was associated with menopausal age. These findings show the importance of lifestyle factors in determining menopausal age.     

Prenatal risk factors for cryptorchidism: a record linkage study

Using data from the Oxford Record Linkage Study (ORLS), we conducted a case–control study to examine prenatal risk factors for cryptorchidism. We identified 1449 boys born during 1970–86 for whom there was a record of an orchidopexy during 1970–87. Up to eight controls were matched to each case on year of birth and hospital or place of delivery. For each boy and his mother we extracted abstracts of maternity and general hospital records from the ORLS. Low birthweight (trend P  < 0.001), low social class (trend P  < 0.001), breech presentation (relative risk 1.67; 95% confidence interval [CI] 1.16, 2.41), pre-eclampsia (1.17 [1.00, 1.37]), artificial feeding (1.22 [1.04, 1.45]) and episiotomy (1.13 [1.00, 1.27]) were identified as independent risk factors for cryptorchidism. Gestational age was not independently associated with cryptorchidism after adjusting for birthweight ( P  = 0.33), and this observation suggested that some cryptorchid boys may have suffered from intra-uterine growth retardation. Low birthweight, breech presentation and pre-eclampsia may have in common poor placental function and impaired fetal growth, which may be causes of cryptorchidism.     

Cancer of the testis, socioeconomic status, and occupation.

The risk of testicular cancer in relation to lifetime histories of socioeconomic status, occupation, and occupational exposures was examined in a case-control study in England. Interviews were conducted with 259 cases, 238 control patients treated at radiotherapy and oncology centres, and 251 controls who were hospital inpatients in other departments. Risk of testicular cancer was raised in men of high socioeconomic status measured both by occupation and in other ways, and was similar in relation to status measured at birth and at various later stages of life. The occupations with highest risk of the tumour were paper and printing workers, professionals, and administrators. Exposures to various specific occupational agents that have been suggested in publications as potential risk factors were examined, but none showed an association with risk. The relative risk for occupational exposure to ionising radiation was 1.62 (95% confidence interval 0.83-3.17).     

Bioterrorism-related anthrax surveillance,Connecticut, September-December, 2001

On November 19, 2001, a case of inhalational anthrax was identified in a 94-year-old Connecticut woman, who later died. We conducted intensive surveillance for additional anthrax cases, which included collecting data from hospitals, emergency departments, private practitioners, death certificates, postal facilities, veterinarians, and the state medical examiner. No additional cases of anthrax were identified. The absence of additional anthrax cases argued against an intentional environmental release of Bacillus anthracis in Connecticut and suggested that, if the source of anthrax had been cross-contaminated mail, the risk for anthrax in this setting was very low. This surveillance system provides a model that can be adapted for use in similar emergency settings.     

Epidemiology of Escherichia coli O157:H7 outbreaks, United States, 1982-2002

Escherichia coli O157:H7 causes 73,000 illnesses in the United States annually. We reviewed E. coli O157 outbreaks reported to Centers for Disease Control and Prevention (CDC) to better understand the epidemiology of E. coli O157. E. coli O157 outbreaks (>or=2 cases of E. coli O157 infection with a common epidemiologic exposure) reported to CDC from 1982 to 2002 were reviewed. In that period, 49 states reported 350 outbreaks, representing 8,598 cases, 1,493 (17%) hospitalizations, 354 (4%) hemolytic uremic syndrome cases, and 40 (0.5%) deaths. Transmission route for 183 (52%) was foodborne, 74 (21%) unknown, 50 (14%) person-to-person, 31 (9%) waterborne, 11 (3%) animal contact, and 1 (0.3%) laboratory-related. The food vehicle for 75 (41%) foodborne outbreaks was ground beef, and for 38 (21%) outbreaks, produce.     

Typical but not "atypical" antipsychotic effects on startle gating deficits in prepubertal rats

RATIONALE: Dopamine (DA) agonists and NMDA antagonists disrupt sensorimotor gating in rats, as measured by a loss of prepulse inhibition of the startle reflex. These effects are used in predictive models for antipsychotic efficacy: clinically "typical" and "atypical" antipsychotics restore PPI in adult rats treated with DA agonists such as apomorphine (APO), while clinically "atypical" antipsychotics restore PPI in rats treated with NMDA antagonists such as phencyclidine (PCP). We previously reported that the PPI disruptive effects of both APO and PCP are evident in 16- to 18-day-old rat pups, suggesting that the brain substrates for these effects are functional very early in development. OBJECTIVE: In the present study we assessed the developmental patterns of antipsychotic effects in these measures. METHODS: The PPI-disruptive effects of APO and PCP, and their antagonism by the typical antipsychotic haloperidol, and the atypical antipsychotic quetiapine, were assessed across development in Sprague-Dawley rats. RESULTS: Similar to the pattern seen in adults, both haloperidol and quetiapine opposed APO-induced PPI deficits in 16- to 19-day-old rat pups. However, the "atypical" antipsychotic quetiapine did not oppose PCP-induced PPI deficits in pups or prepubertal (45 day) adolescents, but did oppose these PCP effects in postpubertal rats. CONCLUSIONS: While brain substrates mediating the PPI-disruptive effects of DA agonists and NMDA antagonists are functional early in development, some physiological event associated with puberty is a necessary condition for the "atypical antipsychotic profile" in this predictive model.     

Ovarian germ cell malignancies in England: epidemiological parallels with testicular cancer.

The epidemiology of germ cell cancer of the ovary has been little investigated. We studied ovarian germ cell cancers incident 1971-84 in England, using data from the England and Wales national cancer register. The age distribution showed a sharp peak at ages 15-19, to which both teratomas and dysgerminomas contributed equally, and a secondary, much wider peak, at ages 65-69, mainly due to teratomas. For teratomas there were diverging secular trends by age: incidence has been increasing at ages 0-44 (P around 0.05) and decreasing at ages over 44 (P less than 0.01). Birth cohort analysis showed an increase in risk at ages 0-44 for more recent generations of women. There were no changes over time for dysgerminomas. There was no clear geographic pattern of distribution across the regions of England. The early age peak, and the increase in incidence of ovarian germ cell cancers at young ages but decrease at older ages, resembles testicular cancer epidemiology. Interestingly, discrepancies and similarities in the age distribution of these tumours between the sexes parallel lifetime profiles of gonadotropin levels in each sex.     

Electroconvulsive therapy in a patient with severe tic and major depressive episode

A patient with a disabling tic and a major depressive episode responded partially to phenelzine, but relapsed after medication was withdrawn because of hypertensive and hepatotoxic reactions. The patient's motor and affective symptoms resolved after electroconvulsive therapy, and he remains asymptomatic after 1 year.     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.