The impact of diabetes on survival among patients with first myocardial infarction

OBJECTIVE - The purpose of this paper is to estimate the impact of diabetes on survival among patients with first acute myocardial infarction, using data from the World Health Organization (WHO) Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) Project in Newcastle, New South Wales, Australia. RESEARCH DESIGN AND METHODS - The WHO MONICA Project is a community-based surveillance system that monitors coronary heart disease morbidity and mortality. All patients with suspected coronary events were observed for 28 days after the onset of symptoms. RESULTS - Of 5,322 patients with acute myocardial infarction and no previous history of ischemic heart disease (3,643 men and 1,679 women), 333 men (9%) and 224 women (13%) had a history of diabetes. The age-adjusted 28-day case fatality for women with diabetes (25%) was significantly higher than for women without diabetes (16%); relative risk 1.56 (95% CI: 1.19-2.04). The difference for men was also significant (25% with diabetes and 20% without diabetes); relative risk 1.25 (95% CI: 1.02-1.53). Age-specific case fatality increased significantly with age in both men and women without diabetes, but systematic age effects were not so apparent in patients with diabetes. Case fatality significantly decreased over the study period in patients without diabetes, but not among the diabetic patients. CONCLUSIONS - The increased risk of death in the diabetic patients remained after accounting for their poorer risk factor profiles; even if they reached the hospital alive, diabetic patients were also less likely to survive than nondiabetic patients. The relative impact of diabetes on survival is greater in women than in men.

Breast cancer five-year survival in New South Wales women, 1972 to 1991

This study of breast cancer survival is based on analysis of five-year relative survival of 38 362 cases of invasive breast cancer in New South Wales (NSW) women, incident between 1972 and 1991, with follow-up to 1992, using data from the population-based NSW Central Cancer Registry. Survival was ascertained by matching the registry file of breast cancers against NSW death certificates from 1972 to 1992, mainly by automated probabilistic linkage. Absolute survival of cases was compared with expected survival of age- and period-matched NSW women. Proportional hazard regression analysis was used for examination of the effects on excess mortality of age, period of diagnosis and degree of spread at diagnosis. Relative survival at five years increased from 70 per cent in 1972-1976 to 77 per cent in 1987-1991. Survival improved during the 1970s and in the late 1980s. Regression analysis suggested that part of the improved survival in the late 1980s was due to lesser degree of spread at diagnosis, whereas the improved survival during the 1970s may have been due to treatment. Survival was better for those aged 40-49 years (RR = 0.86) and worse for those aged greater than or equal to 70 years (RR = 1.22) compared with the referent group (60-69 years). Excess mortality was much less for those with invasive localised disease than those with regional spread (RR = 3.1) or metastatic cancer (RR = 15.5) at diagnosis. For the most recent period (1987-1991), relative five-year survival was 90, 70 and 18 per cent, respectively, for the three degree-of-spread categories.

Breast cancer five-year survival, by New South Wales regions, 1980 to 1991

Breast cancer five-year relative survival was calculated for 16 urban and rural regions in New South Wales (NSW) for cases incident in 1980-1991. Survival analysis employed cancer registry data linked with the death register, and age- and period-matched regional mortality of NSW women, Proportional hazard regression analysis was used to compare excess mortality in breast cancer cases in each region. The effect of region was significant (P < 0.05) in the analysis, after age and the follow-up variable (and their intel action) were adjusted for, although no region was significantly different from the referent group (chosen because of average relative five-year survival). When degree of spread and its interactions were entered into che model, the effect of region became nonsignificant. A significant linear trend (P < 0.05) in the adjusted relative risk for excess mortality in breast cancer cases was noted when regions were divided into quartiles based on socioeconomic status, with higher relative risk in low-socioeconomic-status groups; this effect also disappeared with adjustment for degree of spread at diagnosis. There was no general effect of rurality versus capital city or other metropolitan centres. This study demonstrates a small effect of region of residence and implied socioeconomic status on breast cancer survival in NSW women, but this becomes nonsignificant when the data are adjusted for degree of spread at diagnosis, This suggests that earlier diagnosis would he of benefit in reducing minor inequalities in breast cancer survival in NSW women.

Variation in length, fecundity and survival of pink wax scale, Ceroplastes rubens Maskell (Hemiptera: Coccidae), on umbrella trees

We investigated some of the factors that may lead to outbreaks of pink wax scale, Ceroplastes rubens Maskell, on umbrella trees, Schefflera actinophylla (Endl.). Estimates of birth and death rates of pink wax scale were high and variable within and among trees; variation in these rates was not related to scale density. Adult fecundity correlated significantly but weakly with adult test length; mean fecundity was 292 eggs per female with a range of 5-1178. Adult test length and its variance decreased weakly with increasing density. Field experiments showed that mortality of C. rubens is greatest during the first 24 hours after hatching when approximately half disappear. The rate of loss decreases over time with 0.3% of initial motile first-instar nymphs surviving to maturity. Rates of loss varied significantly between trees, indicating that some trees are more suitable for scale colonisation and survival.

Public choice of species for the ark: Phylogenetic similarity and preferred wildlife species for survival

Humans play a role in deciding the fate of species in the current extinction wave. Because of the previous Similarity Principle, physical attractiveness and likeability, it has been argued that public choice favours the survival of species that satisfy these criteria at the expense of other species. This paper empirically tests this argument by considering a hypothetical ‘Ark’ situation. Surveys of 204 members of the Australian public inquired whether they are in favour of the survival of each of 24 native mammal, bird and reptile species (prior to and after information provision about each species). The species were ranked by percentage of ‘yes’ votes received. Species composition by taxon in various fractions of the ranking was determined. If the previous Similarity Principle holds, mammals should rank highly and dominate the top fractions of animals saved in the hierarchical list. We find that although mammals would be over-represented in the ‘Ark’, birds and reptiles are unlikely to be excluded when social choice is based on numbers ‘voting’ for the survival of each species. Support for the previous Similarity Principle is apparent particularly after information provision. Public policy implications of this are noted and recommendations are given.

Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer

Sporadic colorectal cancer (CRC) characterized by high-level DNA microsatellite instability (MSI-H) has a favorable prognosis. The reason for this MSI-H survival advantage is not known. The aim of this study was to correlate proliferation, apoptosis, and prognosis in CRC stratified by MSI status. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody in a selected series of 100 sporadic colorectal cancers classified according to the level of MSI as 31 MSI-H, 29 MSI-Low (MSI-L), and 40 microsatellite stable (MISS). The Ki-67 index was significantly higher in MSI-H cancers (P < 0.0001) in which the PI was 90.1 1.2% (mean +/- SE) compared with 69.5 +/- 3.1 % and 69.5 +/- 2.3 % in MSI-L and MSS subgroups, respectively. There was a positive linear correlation between the apoptotic index (AI) and PI (r = 0.51; P < 0.001), with MSI-H cancers demonstrating an increased AI:PI ratio indicative of a lower index of cell production. A high PI showed a trend toward predicting improved survival within MSI-H cancers (P = 0.09) but did not predict survival in MSI-L or MSS cancers. The Al was not associated with survival in any MSI subgroup. In conclusion, this is the first study to show that sporadic MSI-H cancers are characterized by a higher AL:PI ratio and increased proliferative activity compared with MSI-L and MSS cancers, and that an elevated PI may confer a survival advantage within the MSI-H subset.

Embryonic development of the nervous system of the temnocephalid flatworm Craspedella pedum

The nervous system of temnocephalid flatworms consists of the brain and three pairs of longitudinal connectives extending into the trunk and tail. The connectives are crosslinked by an invariant number of regularly spaced commissures. Branches of the connectives innervate the tentacles of the head and the sucker organ in the tail. A set of nerve rings encircling the pharynx and connected to the brain and connectives constitute the pharyngeal nervous system. The nervous system is formed during early embryogenesis when the embryo represents a multilayered mesenchymal mass of cells. Gastrulation and the formation of separate epithelial germ layers that characterize most other animal groups are absent. The brain arises as a bilaterally symmetric condensation of postmitotic cells in the deep layers of the anterior region of the embryonic mesenchyme. The pattern of axon outgrowth, visualized by labeling with anti-acetylated tubulin (acTub) antibody, shows marked differences from the pattern observed in other flatworm taxa. in regard to the number of neurons that express the acTub epitope. Acetylated tubulin is only expressed in neurons that form long axon tracts. In other flatworm species, such as the typhloplanoid Mesostoma and the polyclad Imogine, which were investigated by us with the acTub antibody (Hartenstein and Ehlers [2000] Dev. Genes Evol. 210:399-415; Younossi-Hartenstein and Hartenstein [2000] Dev. Genes Evol. 210:383-398), only a small number of pioneer neurons become acTub positive during the embryonic period. By contrast, in temnocephalids, most, if not all, neurons express acTub and form long, large-diameter axons. Initially, the brain commissure, pharyngeal nerve ring, and the connectives are laid down. Commissural tracts and tentacle nerves branching off the connectives appear later. We speculate that the precocious differentiation of the nervous system may be related to the fact that temnocephalids move by muscle action, and possess a massive and complex muscular system when they hatch. In addition, they have muscular specializations such as the anterior tentacles and the posterior sucker that are used as soon as they hatch. By contrast, juveniles of Mesostoma and larvae of polyclads move predominantly by ciliary action that may not require a complex neural circuitry for coordination. (C) 2001 Wiley-Liss, Inc.

The expression of fibroblast growth factors and their receptors in the embryonic and neonatal mouse inner ear

Four different fibroblast growth factor receptors (FGFR) are known, three of which have splice variants (known as the b and c variants) in the FGF-binding domain, to give different patterns of sensitivity to the different FGFs. The expression of the b and c variants of the FGF receptors. together with the expression of the ligands FGF1. FGF2, FGF3, FGF7, FGF8b and FGF8c, was determined by quantitative reverse transcription-polymerase chain reaction in developing whole mouse inner ears, and in dissected components of the postnatal mouse inner ear. At embryonic age (E)10.5 days, when the otocyst is a simple closed sac, the receptor most heavily expressed was FGFR2b, relative to the postnatal day 0 level. Over the period E10.5-E12.5. during which the structures of the inner ear start to form, the expression of the different FGF receptors increased 10(2)-10(4) fold per unit of tissue, and there was a gradual switch towards expression of the 'c' splice variants of FGFR2 and FGFR3 rather than the 'b' variants. At E10.5, the ligands most heavily expressed, relative to the postnatal day 0 level, were FGF3, FGF8b and FGF8c. In the postnatal inner eat. the patterns of expression of receptors and ligands tended to be correlated, such that receptor variants were expressed in the same regions as the ligands that are known to activate them effectively. The neural/sensory region expressed high levels of FGFR3c, and high levels of the ligand FGF8b. The same area also expressed high levels of FGFR1b and FGFR2b, and high levels of FGF3. The lateral wall of the cochlea (including the stria vascularis and the spiral ligament) expressed high levels of FGFR1c and FGF1. 11 is suggested that the different FGF receptors and ligands are expressed in a spatially coordinated pattern to selectively program cochlear development. (C) 2001 Elsevier Science B.V. All rights reserved.

Overexpression of a Slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish

Slit is expressed in the midline of the central nervous system both in vertebrates and invertebrates. In Drosophila, it is the midline repellent acting as a ligand for the Roundabout (Robo) protein, the repulsive receptor which is expressed on the growth cones of the commissural neurons. We have isolated cDNA fragments of the zebrafish slit2 and slit3 homologues and found that both genes start to be expressed by the midgastrula stage well before the axonogenesis begins in the nervous system, both in the axial mesoderm, and slit2 in the anterior margin of the neural plate and slit3 in the polster at the anterior end of the prechordal mesoderm. Later, expression of slit2 mRNA is detected mainly in midline structures such as the floor plate cells and the hypochord, and in the anterior margins of the neural plates in the zebrafish embryo, while slit3 expression is observed in the anterior margin of the prechordal plate, the floorplate cells in the hindbrain, and the motor neurons both in the hindbrain and the spinal cord. To study the role of Slit in early embryos, we overexpressed Slit2 in the whole embryos either by injection of its mRNA into one-cell stage embryos or by heat-shock treatment of the transgenic embryos which carries the slit2 gene under control of the heat-shock promoter. Overexpression of Slit2 in such ways impaired the convergent extension movement of the mesoderm and the rostral migration of the cells in the dorsal diencephalon and resulted in cyclopia. Our results shed light on a novel aspect of Slit function as a regulatory factor of mesodermal cell movement during gastrulation. (C) 2001 Academic Press.

Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways

We show here that the neurotrophin nerve growth factor (NGF), which has been shown to be a mitogen for breast cancer cells, also stimulates cell survival through a distinct signaling pathway. Breast cancer cell lines (MCF-7, T47-D, BT-20, and MDA-MB-231) were found to express both types of NGF receptors: p140(trkA) and p75(NTR). The two other tyrosine kinase receptors for neurotrophins, TrkB and TrkC, were not expressed. The mitogenic effect of NGF on breast cancer cells required the tyrosine kinase activity of p140(trkA) as well as the mitogen-activated protein kinase (MAPK) cascade, but was independent of p75(NTR). I, contrast, the anti-apoptotic effect of NGF (studied using the ceramide analogue C2) required p75(NTR) as well as the activation of the transcription factor NF-kB, but neither p140(trkA) nor MAPK was necessary. Other neurotrophins (BDNF, NT-3, NT-4/5) also induced cell survival, although not proliferation, emphasizing the importance of p75(NTR) in NGF-mediated survival. Both the pharmacological NF-KB inhibitor SN50, and cell transfection with IkBm, resulted in a diminution of NGF anti-apoptotic effect. These data show that two distinct signaling pathways are required for NGF activity and confirm the roles played by p75(NTR) and NF-kappaB in the activation of the survival pathway in breast cancer cells.

It's the first bites that count: Survival of first-instar monarchs on milkweeds

Mortality of first instars is generally very high, but variable, and is caused by many factors, including physical and chemical plant characters, weather and natural enemies. Here, a summary of detailed field-based studies of the early-stage survival of a specialist lepidopteran herbivore is presented. First-instar larvae of the monarch butterfly, Danaus plexippus, a milkweed specialist, generally grew faster and survived better on leaves when latex flow was reduced by partial severance of the leaf petiole. The outcome depended on milkweed species, and was related to the amount of latex produced, as well as other plant characters, such as leaf hairs, microclimate and concentration of secondary metabolites. Even for a so-called 'milkweed specialist', larval performance and survival appears to be related to the concentration of cardenolides produced by the plants (a potential chemical defence against herbivory). This case study of monarchs and milkweeds highlights the need for field-based experiments to assess the effect of plant characters on the usually poor survival of early instar phytophagous insects. Few similar studies concerning the performance and survival of first-instar, eucalypt-specific herbivores have been conducted, but this type of study is considered essential based on the findings obtained using D. plexippus.