Development of an auxotrophic oral live Shigella flexneri vaccine

An oral live attenuated Shigella flexneri vaccine candidate strain was constructed by making it auxotrophic and dependent on aromatic metabolites not available in mammalian tissues. An aroD gene of Escherichia coli K12 strain NK 5131, inactivated by insertion in it of the Tn 10 transposon, was transduced using phage P1 into a virulent S. flexneri serotype Y strain (Sfl 1) isolated from a patient with bacillary dysentery. One of the transductant strains Sfl 114 was found to invade HeLa cells in vitro, to cause plaque formation in HeLa monolayers (i.e. maintain intracellular multiplication in vitro), but to be unable to cause keratoconjunctivitis in guinea-pig eyes. When the strain was fed to Macacca fascicularis monkeys it was well tolerated, excreted for 1-4 days, and found to elicit a local intestinal sIgA and serum IgA, IgM and IgG responses. Monkeys challenged with 100 ID50 dose (1 X 10(11) bacteria) of the virulent parent Sfl 1 strain were completely protected from development of diarrhoea. Coloscopy of the monkeys and the sampling of intestinal biopsies showed that the vaccine protected against the surface epithelial erosions and ulcerations seen in unimmunized monkeys. Killing of invading virulent shigellae apparently took place intracellularly in the mucosa suggesting that cellular immune mechanisms played a role in the elicited host defence. The constructed S. flexneri Sfl 114 strain has the properties of a promising shigella vaccine and will next be the subject of studies with human volunteers.     

Changing mortality patterns in Nauruans: an example of epidemiological transition.

An analysis of mortality data for the years 1982-5 was carried out for the Micronesian population (aged 15 years and over) of the central Pacific Island, Nauru. Among males, the most common causes of death were circulatory system disorders (33.3%), accidents (25.2%), and diabetes mellitus (12.1%). The majority of accidents occurred in the 15-34 year age group and involved motor vehicles. Among females, neoplasms (almost all lung and cervix) (22.4%), circulatory system disorders (20.7%), and diabetes mellitus (17.2%) were the most common causes of death. When accidents are excluded, 59.4% of deaths were in persons with diabetes. Compared with Australia, mortality rates in almost all age groups were at least five times higher for males and females for a comparable period. Nauruan life expectancy (39.5 years for men and 48.5 years for women) is one of the lowest in the world. These data confirm the high mortality associated with diabetes mellitus in Nauruans as evidenced in earlier studies. Modernization of this society through the affluence acquired by the mining of phosphate has led to serious public health problems relating to non-communicable diseases so that the mortality trends now mirror those of developed societies.     

Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

The Framingham Disability Study: physical disability among community-dwelling survivors of stroke

The relationship between stroke and physical disability was examined in a cohort of adult, Framingham, Massachusetts, residents who, between 1948 and 1951, were assembled for a longitudinal examination of cardiovascular disease. Multivariate analyses examined the amount of residual disability attributable to stroke among 2540 community-dwelling survivors, 27 years after their initial examination, after controlling for age, cardiovascular risk factors, other cardiovascular diseases, and eight general health conditions related to physical disability. Among men living in the community, a history of stroke explained 12% of the variance in physical disability. Suffering a stroke, however, was not as strongly related to physical disability among women living in the community, accounting for only 3% of the variance. Results suggest that although older men and women die from the same major causes, they may not be disabled by the same conditions.     

Dietary intake of healthy subjects before and one year after dietary advice

This study was conducted to follow up healthy subjects from a previous study (Warwick & Williams, 1987) in which favourable dietary changes were achieved during 1 week immediately after dietary advice but were accompanied by reduced energy intakes and weight loss. Twenty-one subjects (8m, 13f; 57 per cent of the original group) participated in the follow-up study. Dietary intakes were measured using 7-d weighed records on three occasions: before, immediately after and 1 year after receiving dietary advice. Intakes 1 year after dietary advice continued to show some of the favourable changes observed immediately after the advice but were not accompanied by reduced energy intakes and weight loss. Intakes before, immediately after, and 1 year after dietary advice respectively were: energy, 9.0, 7.8 and 8.9 MJ/d (2150, 1860 and 2120 kcal/d); fat, 36.9, 32.9 and 31.5 per cent of total energy; carbohydrate, 44.2, 47.9 and 49.6 per cent of total energy; dietary fibre, 32, 36 and 36 g/d; sodium, 116, 97 and 110 mmol/d; and Na:K ratio, 1.4, 1.2 and 1.2 mmol. Nutrient densities for fibre and most micronutrients tended to be higher 1 year after dietary advice than before, but were highest immediately after the advice. Nutrient densities for sodium and total sugars did not vary between the 3 study weeks. It was concluded that our healthy subjects adapted their intakes to maintain energy balance while retaining favourable dietary changes for at least 1 year after dietary advice.     

Eledoisin and lacrimal secretion in the rabbit

Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine.